What is the role of montelukast (leukotriene receptor antagonist) or zafirlukast (leukotriene receptor antagonist) in treating atopic dermatitis (AD) in patients, particularly those with co-existing asthma or allergic rhinitis?

Leukotriene Receptor Antagonists for Atopic Dermatitis

Montelukast and zafirlukast are NOT recommended for the treatment of atopic dermatitis based on the most recent and authoritative guidelines, which explicitly state there is insufficient evidence to support their use. 1

Guideline Position

The 2024 American Academy of Dermatology guidelines definitively conclude that there are insufficient data to make a recommendation regarding the use of montelukast in the management of atopic dermatitis. 1 This represents the highest quality guideline evidence available and should guide clinical decision-making.

The 2014 AAD guidelines similarly do not include leukotriene receptor antagonists among recommended systemic therapies for atopic dermatitis, focusing instead on cyclosporine, azathioprine, and other immunomodulators. 1

Research Evidence Shows Conflicting Results

While guidelines do not support their use, the research literature presents mixed findings:

Negative Evidence (Higher Quality):

• A 2007 randomized, double-blind, placebo-controlled trial in 60 adults with moderate atopic dermatitis found no significant benefit of montelukast 10 mg daily over placebo after 8 weeks of treatment. 2
• The improvement in SASSAD scores was actually marginally superior in the placebo group (1.76 points) compared to montelukast (1.41 points). 2

Positive Evidence (Lower Quality):

• A small 2001 crossover study (n=8) showed modest but statistically significant improvement with montelukast as adjunctive therapy. 3
• A 2001 open-label trial found montelukast comparable to combination therapy in 32 adults. 4
• Case reports describe successful treatment in severe cases, particularly when corticosteroids were contraindicated. 5

Clinical Context: When Leukotriene Antagonists May Be Considered

The only scenario where these agents might have a role is in patients with atopic dermatitis AND concurrent asthma or allergic rhinitis, where the primary indication is treating the respiratory condition. 1

• One pediatric study (n=25) demonstrated decreased self-reported sleep disturbance in children with atopic dermatitis treated with montelukast, though further research was deemed necessary. 1
• In patients with both asthma and allergic rhinitis, zafirlukast combined with intranasal budesonide was more effective for controlling bronchial symptoms than antihistamine combinations. 1

Recommended Treatment Algorithm for Atopic Dermatitis

Instead of leukotriene antagonists, use the following evidence-based approach:

1. First-line: Emollients plus topical corticosteroids and/or topical calcineurin inhibitors 1

2. Second-line (refractory cases): Phototherapy (narrowband UVB) 1

3. Third-line (severe, refractory disease): Systemic immunomodulators in this order of preference:

   • Dupilumab or tralokinumab (biologics with high-certainty evidence for efficacy) 1
   • Cyclosporine 3-5 mg/kg/day (limited to 1 year duration) 1
   • Azathioprine 1-3 mg/kg/day 1
   • Mycophenolate mofetil 1

Critical Pitfalls to Avoid

• Do not prescribe montelukast or zafirlukast specifically for atopic dermatitis treatment, as this contradicts current guideline recommendations and lacks sufficient evidence. 1
• If a patient with atopic dermatitis is already taking a leukotriene antagonist for asthma, do not expect significant improvement in their skin disease based on this medication alone. 2
• Do not delay appropriate systemic immunomodulatory therapy (dupilumab, cyclosporine, azathioprine) in favor of an unproven leukotriene antagonist trial. 1

Special Population: Concurrent Asthma

If the patient has both atopic dermatitis and asthma, treat each condition according to its respective guidelines:

• For asthma: Low-dose inhaled corticosteroids are preferred over leukotriene antagonists 6, 7
• For atopic dermatitis: Follow the algorithm above 1
• Montelukast or zafirlukast may be used as alternative asthma therapy (not first-line), but should not be expected to significantly improve the atopic dermatitis. 6, 7, 2