What are the treatment approaches for urticaria and angioedema?

What is AAS in the Era of Urticaria and Angioedema

AAS (anabolic androgenic steroids) are the treatment of choice for most adults with C1 esterase inhibitor deficiency (hereditary angioedema), but they have no role in treating ordinary urticaria or angioedema and should be avoided in children with hereditary angioedema due to virilizing side-effects. 1

Understanding the Context: AAS vs. ASA

It's critical to distinguish between:

• AAS (Anabolic Androgenic Steroids): Used specifically for hereditary angioedema maintenance therapy 1
• ASA (Aspirin): A drug that should be avoided in urticaria patients as it can worsen symptoms 1

When AAS Are Indicated: Hereditary Angioedema Only

Diagnostic Approach

• Screen with serum C4 levels in patients presenting with recurrent angioedema without wheals, as low C4 (<30% mean normal) has very high sensitivity for C1 inhibitor deficiency 1
• Confirm diagnosis with quantitative and functional C1 inhibitor assays if C4 is low 1
• Type I hereditary angioedema shows low immunochemical and functional C1 inhibitor, while Type II shows only low functional activity 1

AAS Treatment Protocol for Hereditary Angioedema

• Anabolic steroids are first-line maintenance therapy for symptomatic recurring angioedema or related abdominal pain in adults 1
• Use only low doses for long-term maintenance, but virilizing side-effects may still occur 1
• Mandatory monitoring: Regular liver function tests and imaging for hepatocellular adenomas is essential due to hepatotoxicity risk 1
• Avoid in children whenever possible due to virilizing effects 1

Alternative Maintenance Options for Hereditary Angioedema

• Tranexamic acid may be used instead of anabolic steroids, but is contraindicated in patients with thrombosis history 1
• Regular eye examinations and liver function tests are required with long-term tranexamic acid use 1
• For acute attacks or surgical prophylaxis, C1 inhibitor concentrate is preferred over maintenance therapy 1

When AAS Are NOT Indicated: Ordinary Urticaria and Angioedema

First-Line Treatment: Second-Generation H1-Antihistamines

• Non-sedating H1-antihistamines are the mainstay of therapy for chronic urticaria with or without angioedema 1, 2
• Start with standard doses and increase up to 4-fold if inadequate response after 2-4 weeks 2, 3
• Over 40% of patients show good response to antihistamines alone 1

Second-Line Treatment Algorithm

• Add H2-antihistamines or antileukotrienes for resistant cases 1, 2
• Consider combining different second-generation H1-antihistamines as individual responses vary 2
• Omalizumab 300mg subcutaneously every 4 weeks is indicated for chronic spontaneous urticaria inadequately controlled by antihistamines 2, 3, 4
• Allow up to 6 months for omalizumab response before considering treatment failure 2, 3

Corticosteroid Use: Short-Term Only

• Restrict oral corticosteroids to short courses (3-4 weeks) for severe acute urticaria or life-threatening angioedema 1, 2
• More prolonged treatment may be necessary for delayed pressure urticaria or urticarial vasculitis 1, 2
• Long-term corticosteroids should not be used except in very selected cases under specialist supervision 2

Critical Pitfalls to Avoid

Drugs That Worsen Urticaria

• Avoid aspirin (ASA) and NSAIDs in urticaria patients, as they inhibit cyclooxygenase and can exacerbate symptoms 1, 3
• Avoid codeine, which can trigger histamine release 1, 3
• ACE inhibitors must be avoided in patients with angioedema without wheals and used cautiously when angioedema accompanies urticaria 1, 3
• Avoid oestrogens in hereditary angioedema patients 1

Common Prescribing Errors

• Do not confuse anabolic steroids (for hereditary angioedema) with corticosteroids (short-term use only in ordinary urticaria) 1, 2
• Do not use sedating antihistamines preferentially, as they alter REM sleep patterns without superior efficacy compared to non-sedating agents 5
• Do not use topical steroids routinely for urticaria, as they are not recommended 1

Monitoring Requirements

• For patients on anabolic steroids (hereditary angioedema): Monitor liver function and screen for hepatocellular adenomas regularly 1
• For patients on cyclosporine (severe refractory urticaria): Monitor blood pressure and renal function every 6 weeks 2
• Use validated tools like the Urticaria Control Test (UCT) to objectively assess disease control 3