Atopic dermatitis and skin disease
Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis

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Background

Genetic defects leading to skin barrier dysfunction were recognized as risk factors for atopic dermatitis (AD). It is essential that drugs applied to patients with AD restore the impaired epidermal barrier to prevent sensitization by environmental allergens.

Objectives

We investigated the effect of 2 common treatments, a calcineurin inhibitor and a corticosteroid, on the skin barrier.

Methods

In a randomized study 15 patients with AD were treated on one upper limb with pimecrolimus and on the other with betamethasone twice daily for 3 weeks.

Results

Stratum corneum hydration and transepidermal water loss, a marker of the inside-outside barrier, improved in both groups. Dye penetration, a marker of the outside-inside barrier, was also reduced in both drugs. Electron microscopic evaluation of barrier structure displayed prevalently ordered stratum corneum lipid layers and regular lamellar body extrusion in pimecrolimus-treated skin but inconsistent extracellular lipid bilayers and only partially filled lamellar bodies after betamethasone treatment. Both drugs normalized epidermal differentiation and reduced epidermal hyperproliferation. Betamethasone was superior in reducing clinical symptoms and epidermal proliferation; however, it led to epidermal thinning.

Conclusion

The present study demonstrates that both betamethasone and pimecrolimus improve clinical and biophysical parameters and epidermal differentiation. Because pimecrolimus improved the epidermal barrier and did not cause atrophy, it might be more suitable for long-term treatment of AD.

Section snippets

Patients and treatment regimens

Fifteen patients with mild-to-moderate AD (according to Hanifin and Rajka criteria) and a target lesion score of 3 to 8 (on a scale of 0-12) for both right and left target lesions, and symmetric AD lesions (not differing >1 point between the right and left sides) affecting the upper limbs by at least 10% were treated twice daily for 3 weeks on 1 upper limb with 1% pimecrolimus cream and on the other upper limb with 0.1% betamethasone valerate cream in a double-blind manner. Follow-up

Clinical assessment and stratum corneum hydration

Clinical assessments were performed before the treatment period (day 1), during the treatment period (days 8, 15, and 22), and after a 1-week follow-up period (day 29) to correlate clinical response with possible alterations in skin barrier function. On day 8, considerable clinical improvement was seen after treatment with both betamethasone and pimecrolimus, as assessed by using the pEASI, which includes erythema, infiltration, excoriation, and lichenification. Symptoms of patients treated

Discussion

It has now become clear that defects in the epidermal barrier might be as important as immune dysregulation, which has long been considered the primary cause of AD. It has recently been proposed that inflammation in patients with AD results from inherited and acquired insults to the barrier, and the therapeutic implications of this paradigm have been discussed.36 Repair of the epidermal barrier might become an important objective in the development of new drugs for the treatment of AD. Hence it

References (52)

  • E. Proksch et al.

    Skin barrier function, epidermal proliferation and differentiation in eczema

    J Dermatol Sci

    (2006)
  • I. Jakasa et al.

    Altered penetration of polyethylene glycols into uninvolved skin of atopic dermatitis patients

    J Invest Dermatol

    (2007)
  • M.D. Howell et al.

    Cytokine modulation of atopic dermatitis filaggrin skin expression

    J Allergy Clin Immunol

    (2007)
  • W. Hoetzenecker et al.

    Corticosteroids but not pimecrolimus affect viability, maturation and immune function of murine epidermal Langerhans cells

    J Invest Dermatol

    (2004)
  • P.M. Elias et al.

    Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside pathogenic mechanisms

    J Allergy Clin Immunol

    (2008)
  • U. Hengge et al.

    Adverse effects of topical glucocorticosteroids

    Am Acad Dermatol

    (2006)
  • B.E. Kim et al.

    Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6

    Clin Immunol

    (2008)
  • I.R. Scott et al.

    Filaggrin breakdown to water binding compounds during development of the rat stratum corneum is controlled by the water activity of the environment

    Dev Biol

    (1986)
  • K. Aalto-Korte

    Improvement of skin barrier function during treatment of atopic dermatitis

    J Am Acad Dermatol

    (1995)
  • P.M. Elias et al.

    Structural and lipid biochemical correlates of the epidermal permeability barrier

    Adv Lipid Res

    (1991)
  • J.S. Kao et al.

    Short-term glucocorticoid treatment compromises both permeability barrier homeostasis and stratum corneum integrity: inhibition of epidermal lipid synthesis accounts for functional abnormalities

    J Invest Dermatol

    (2003)
  • C.N. Palmer et al.

    Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

    Nat Genet

    (2006)
  • A. Ruether et al.

    Filaggrin loss-of-function variant contributes to atopic dermatitis risk in the population of Northern Germany

    Br J Dermatol

    (2006)
  • P.M. Elias et al.

    Does the tail wag the dog? Role of the barrier in the pathogenesis of inflammatory dermatoses and therapeutic implications

    Arch Dermatol

    (2001)
  • M. Fartasch et al.

    Disturbed extruding mechanism of lamellar bodies in dry non-eczematous skin of atopics

    Br J Dermatol

    (1992)
  • J.L. Sugarman et al.

    The objective severity assessment of atopic dermatitis score: an objective measure using permeability barrier function and stratum corneum hydration with computer-assisted estimates for extent of disease

    Arch Dermatol

    (2003)
  • Cited by (0)

    Supported by grants of the Deutsche Forschungsgemeinschaft (SFB415/B2 and SFB617/A7, A21) and Novartis Pharma, Nürnberg (Germany), given to E. Proksch and J.-M. Jensen. T. Schwarz and E. Proksch have acted as consultants to Novartis. M. Bräutigam is employed by Novartis.

    Disclosure of potential conflict of interest: J.-M. Jensen has received a travel grant from Novartis. T. Schwarz has received grants from Novartis and Therakos and has served as an advisor for Novartis. The rest of the authors have declared that they have no conflict of interest.

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