Modulation of Atopy Patch Test and Skin Prick Test by Pretreatment with 1% Pimecrolimus Cream

Abstract

Background: In a subgroup of patients with atopic eczema (AE), aeroallergens are relevant eliciting factors. The atopy patch test (APT) was proposed as inflammation model for AE. Objective: It was the aim of this study to investigate the effect of pretreatment with 1% pimecrolimus cream (Elidel^®) on the APT and skin prick test (SPT). Methods: In a randomized, controlled, double-blind study, 20 patients with AE and positive SPT and APT screening reaction to house dust mite Dermatophagoides pteronyssinus, cat dander, grass or birch pollen were enrolled (age 20 ± 11 years, 55% males). For 2 weeks, patients twice daily applied pimecrolimus and vehicle control to marked fields on their backs and forearms. Then, APT was performed (200 index of reactivity/g extracts in petrolatum; Stallergènes, France) on both fields on the back and SPT was performed on the pretreated forearms. Results: Including only patients with different readings (n = 13), stronger APT suppression of at least 1 ETFAD (European Task Force on Atopic Dermatitis) grade in the pimecrolimus area versus intraindividual control was observed in 10 of these patients after 48 and 72 h (p < 0.05; 90% CI 50.5–93.4). Including all 20 subjects, the analysis still showed a borderline significance compared with the vehicle (p = 0.0564). SPT with histamine and aeroallergens showed a median 7.5–10% reduction in actively pretreated areas (p = 0.086). Immunohistochemical analysis in 2 patients revealed an induction of interferon-γ in primecrolimus-pretreated skin. Conclusion: APT can be used as a model for AE skin inflammation. It was shown for the first time that pimecrolimus pretreatment has a potential to suppress the development of lesions induced by aeroallergen exposure in patients with AE.

Pimecrolimus, a topical calcineurin inhibitor used in the treatment of atopic eczema

“…In summary, a satisfactory therapy of chronic inflammatory disease such as AE should reduce symptoms, prevent relapses/flares and provide long-term management with high safety also for children. [64][65][66][67]63,[68][69][70] 3. Introduction to the compound SDZ ASM 981, an ascomycin derivate, is a compound in a novel class of anti-inflammatory macrolactams developed more than 20 years ago --known today as pimecrolimus, a calcineurin inhibitor.…”

“…After 3 years, Weissenbacher et al showed that pimecrolimus pretreatment has a potential to suppress the development of lesions induced by aeroallergens exposure in patients with AE [70]. Following these facts, Wollenberg et al suggested the proactive therapy of AE, 'an emerging concept', by using topical TCIs several times a week resulting in less disease exacerbation and better quality of life [71].…”

Immunoglobulin E-Mediated Allergy Plays a Role in Atopic Eczema as Shown in the Atopy Patch Test

“…The development of a standardized APT for food allergy is a future plan, as well as a study on the mechanisms of APT reactions involving both patients with intrinsic and extrinsic AE and investigating the role of the Fc ε receptor I and allergen-specific T-cell populations. Furthermore, the APT will be used in trials on topical and systemic therapy for AE and is evaluated as itch model [70,71]. Other aeroallergens of regional significance are to be standardized.…”

Atopic Dermatitis in 2008

“…Having stated the central role of topical corticosteroids, we must also recognize the substantial benefits we gained from topical calcineurin inhibitors [140][141][142][143][144][145][146][147][148][149]. In the last few years, the medical community has gained much understanding on this group of medications regarding its desirable actions and potential side effects [140][141][142][143][144][145][146][147][148][149].…”

“…In the last few years, the medical community has gained much understanding on this group of medications regarding its desirable actions and potential side effects [140][141][142][143][144][145][146][147][148][149]. Specifically, these inhibitors improved skin inflammation in patients with atopic dermatitis, likely through the mechanisms of regulatory T cell correction [141], depletion of plasmacytoid dendritic cells [142], suppressing expressions of the cytokine IL-5, the chemokines eotaxin and RANTES, and the chemokine receptor CCR3 [145], induction of apoptosismediated T cell depletion [146], reduction of dermal infiltration of cytokineexpressing inflammatory cells [147,148], and suppression of skin response to aeroallergens [143], while at the same time they do not appear to hinder the immune system to respond to vaccination [140,149]. The recent 'black box' warning label placed by the FDA on these inhibitors casts a cloud for the longterm use of this group of medications.…”