University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• In the treatment of atopic dermatitis in children, are there more effective treatments for facial lesions than hydrocortisone?

Clinical Bottom Lines

1. Topical tacrolimus is more effective than hydrocortisone for treatment of atopic dermatitis.
2. Topical tacrolimus has the added benefits of avoiding the steroid-induced local adverse effects such as cutaneous atrophy, striae, telangiectasia, dyspigmentation, and perioral dermatitis and is safe for long term use.
3. Topical tacrolimus is safe for eyelid application and does not have the associated steroid risks of cataract and glaucoma formation.
4. Topical tacrolimus is significantly more expensive than topical corticosteroids ($112 for a 60 g tube, but covered by most insurances).
   

Summary of Key Evidence

1. Randomized double-blind control trial comparing 0.03% and 0.1% tacrolimus and 1% hydrocortisone in regards to efficacy and safety of atopic dermatitis treatment in pediatric population 2-15 years old.¹
2. Inclusion criteria required 5-60% total body surface area involvement -- classified as moderate to severe atopic dermatitis.
3. Exclusion criteria were serious skin disorders other than atopic dermatitis requiring treatment or patients with a history of eczema herpeticum. Other prohibited therapies during the study were topical and systemic corticosteroids, antimicrobials and antihistamines, coal tar, topical NSAIDS, nonsteroidal immunosuppressants, UV light treatments, sedatives, or other investigational drugs.
4. 560 patients were randomized into one of three treatment groups: 0.03% tacrolimus, 0.1% tacrolimus, or 1% hydrocortisone. Patient demographics and baseline characteristics similar across treatment groups including most patients having active disease on face and neck; however, the hydrocortisone group did have a longer duration of current episode than either tacrolimus treatment group (question of more treatment resistant atopic dermatitis).
5. Treatment involved a thin layer of ointment applied twice daily to actively diseased areas and treatment was to be stopped 7 days after clearance.
6. Efficacy based on mEASI (modified eczema area and severity index) which was calculated using erythema, edema-induration-papulation, excoriations, lichenification, total body surface area affected, and patient rated intensity of itching.
7. Efficacy rates in 0.3% tacrolimus was a median improvement of 55.2%, in 0.1% tacrolimus was 60.2% and in 1% hydrocortisone was 36%. Separate analysis of head and neck showed respective improvements of 62.5% (0.3% tacrolimus), 75.2% (0.1% tacrolimus), and 43.3% (1% hydrocortisone).
8. Venous tacrolimus levels were never as high as 5ng/ml indicating minimal systemic absorption.
9. Tacrolimus treatment groups showed higher incidence of transient skin burning.
10. All treatment groups showed significant rates of relapse 2 weeks after discontinuation of therapy (only half of the patients maintained a moderate improvement after 2 weeks without therapy).

Additional Comments

• Kang et al shows tacrolimus to be safe and effective (with similar side effect profiles and no tachyphylaxis noted) for up to 1 year of continuous use. Transient burning typically lasted 10 minutes and was most severe in first 4 days of treatment.²
• Paller et al corroborated the safety and efficacy of tacrolimus in the treatment of atopic dermatitis in pediatric patients with 3 months of continuous treatment.³
  

Citation

1. Reitamo S, Van Leent EJM, Ho V et al. Efficacy and safety of tacrolimus ointment compared with that of hydrocortisone acetate ointment in children with atopic dermatitis. J Allergy and Clin Immunol 2002; 109:539-546.
2. Kang S et al. Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children. J Am Acad Dermatol 2001; 44(1 Suppl): S58-64.
3. Paller A et al. A 12-week study of tacrolimus ointment for the treatment of atopic dermatitis in pediatric patients. J Am Acad Dermatol 2001; 44(1 Suppl): S47-57.

CAT Author: Suparna Mullick, MD

CAT Appraisers: Jon Fliegel, MD

Date appraised: November 5, 2003