Onset of pruritus relief with pimecrolimus cream 1% in adult patients with atopic dermatitis: a randomized trial

BACKGROUND: Pimecrolimus cream 1% (Elidel, Novartis Pharmaceuticals AG) effectively improves/relieves pruritus associated with atopic dermatitis (AD), but few data are available regarding the timing of relief. The purpose of this study was to investigate the timing of pruritus relief produced with pimecrolimus in adults with mild/moderate AD and moderate/severe pruritus. METHODS: Patients were randomized to 7 days of treatment with pimecrolimus (n = 100) or vehicle (n = 98). Pruritus severity was assessed daily on a 4-point scale (0 = absent, 3 = severe), reflecting the previous 24 h experience. Patients who completed this core study were eligible to enter a voluntary 5-week, open-label extension study. RESULTS: A significant effect was noted within 48 h of treatment, with pruritus improving in 56% of pimecrolimus-treated patients and 34% of vehicle-treated patients (P = 0.003). Pruritus relief was maintained during the remainder of the core and extension phases, and was accompanied by an improvement in the Investigator's Global Assessment score. CONCLUSION: Pimecrolimus cream 1% significantly reduced pruritus within 48 h.     

Elidel (pimecrolimus) cream 1%: a nonsteroidal topical agent for the treatment of atopic dermatitis

Elidel is a steroid-free cream containing a 1% strength of the topical immunomodulator pimecrolimus. Elidel was specifically developed as a treatment for atopic dermatitis (AD) and is approved for use in children as young as 2 years of age. The production of inflammatory cytokines by activated T cells in skin is thought to play an important role in the pathogenesis of AD. Elidel potently suppresses cytokine production by dermal T cells without significantly impairing systemic immune responses. Elidel does not cause steroid-associated local effects, such as dermal atrophy, striae, or telangiectasia. In randomized controlled clinical studies, twice-daily application of Elidel was shown to significantly improve the signs and symptoms of AD in infants, children, and adults. The clinical effect of Elidel on pruritus, the most troublesome symptom of AD, can be observed within 1 week of therapy and is maintained for the duration of treatment. Elidel is well tolerated; the risk of application-site reactions, such as itching or burning, is comparable with that of the vehicle. Adverse effects were generally mild in patients receiving Elidel and occurred at rates comparable with those in patients receiving vehicle treatment. In a 1-year study, Elidel significantly reduced the incidence of flares when used at the first signs and symptoms of acute AD. As a result, overall corticosteroid use to treat flares was significantly lower in patients using Elidel for early intervention.     

Modulation of atopy patch test and skin prick test by pretreatment with 1% pimecrolimus cream

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-gamma 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.     

Treatment of facial seborrheic dermatitis with pimecrolimus cream 1%: an open-label clinical study in Korean patients

Pimecrolimus cream 1% has shown to be effective in patients with a variety of inflammatory cutaneous disorders. And it might be a useful modality in the treatment of seborrheic dermatitis. This prospective study was aimed at assessing the efficacy and tolerability of pimecrolimus cream 1% in the treatment of facial seborrheic dermatitis. Twenty patients were instructed to apply pimecrolimus cream 1% for 4 consecutive weeks. Assessment of the disease severity was performed at baseline and at week 1, 2, and 4. Clinical assessments of erythema, scaling, and pruritus were measured using a 4-point scale (0-3). Global assessments of the disease severity by patients and investigators were performed at each visit. Mean clinical scores of erythema, scaling, and pruritus significantly improved by 87.4%, 91.9%, and 91.5% respectively at week 4 (p<0.001). Improvements in the global assessment of disease severity determined by patients and investigators also showed excellent results. No specific adverse events other than transient burning and tingling sensations were noted. The relapse of facial seborrheic dermatitis was mostly observed between 3 to 8 weeks after the discontinuation of pimecrolimus. We suggest that the topical application of pimecrolimus cream 1% can be an effective and safe alternative for treatment of facial seborrheic dermatitis.     

Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial

BACKGROUND: Probiotic bacteria are suggested to reduce symptoms of the atopic eczema/dermatitis syndrome (AEDS) in food-allergic infants. We aimed to investigate whether probiotic bacteria have any beneficial effect on AEDS. METHODS: Follow-up of severity of AEDS by the Severity Scoring of Atopic Dermatitis (SCORAD) index in 230 infants with suspected cow's milk allergy (CMA) receiving, in a randomized double-blinded manner, concomitant with elimination diet and skin treatment, Lactobacillus GG (LGG), a mixture of four probiotic strains, or placebo for 4 weeks. Four weeks after the treatment, CMA was diagnosed with a double-blind placebo-controlled (DBPC) milk challenge in 120 infants. RESULTS: In the whole group, mean SCORAD (at baseline 32.5) decreased by 65%, but with no differences between treatment groups immediately or 4 weeks after the treatment. No treatment differences were observed in infants with CMA either. In IgE-sensitized infants, however, the LGG group showed a greater reduction in SCORAD than did the placebo group, -26.1 vs-19.8 (P=0.036), from baseline to 4 weeks after the treatment. Exclusion of infants who had received antibiotics during the study reinforced the findings in the IgE-sensitized subgroup. CONCLUSION: Treatment with LGG may alleviate AEDS symptoms in IgE-sensitized infants but not in non-IgE-sensitized infants.     

The allergic sensitization in infants with atopic eczema from different countries

Background:  No study has compared allergic sensitization patterns in infants with atopic eczema from different countries. The aim of this study was to investigate the patterns of allergic sensitization in a cohort of infants with atopic eczema participating in a multicentre, international study.
Methods:  Two thousand one hundred and eighty-four infants (mean age 17.6 months) with atopic eczema from allergic families were screened in 94 centres in 12 countries to participate in a randomized trial for the early prevention of asthma. Clinical history, Severity Scoring of Atopic Dermatitis Index, measurements for total serum IgE and specific IgE antibodies to eight food and inhalant allergens were entered into a database before randomization to treatment. A history of type of feeding in the first weeks of life and exposure to animals was recorded.
Results:  A total of 52.9% of the infants had raised total IgE, and 55.5% were sensitized to at least one allergen. There was a wide difference in the total IgE values and in the sensitization rates to foods and aeroallergens among infants from different countries. The highest prevalence rates of allergen-sensitized infants were found in Australia (83%), the UK (79%) and Italy (76%). Infants from Belgium and Poland consistently had the lowest sensitization rates. In each country, a characteristic pattern of sensitization was found for aeroallergens (house dust mite > cat > grass pollen >  Alternaria ), but not for food allergens.
Conclusions:  In infants with atopic eczema, there is a wide variation in the pattern of allergic sensitization between countries, and data from one country are not necessarily generalizable to other countries.     

Long-term management of atopic dermatitis in infants with topical pimecrolimus,a nonsteroid anti-inflammatory drug

BACKGROUND: Pimecrolimus cream 1% (Elidel, SDZ ASM 981), a nonsteroid selective inhibitor of inflammatory cytokines, is effective in the treatment of atopic dermatitis (AD). In this study we compared early intervention with pimecrolimus cream with treatment with a vehicle control. OBJECTIVE: The purpose of this investigation was to assess whether early treatment in infants of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares. METHODS: In this 1-year, double-blind controlled study, 251 infants aged 3 to 23 months with AD were randomized 4:1 to a pimecrolimus-based regimen (n = 204) or a conventional treatment regimen (n = 47). Both groups used emollients for dry skin. Early AD signs and symptoms were treated either with pimecrolimus cream to prevent flares or, in the control group, with vehicle. Vehicle was used to maintain blinding conditions. In the event of flares, moderately potent corticosteroid was permitted in both groups. The primary efficacy end point was the incidence of flares at 6 months. RESULTS: Pimecrolimus significantly reduced the incidence of flares compared with control treatment (P <.001), with 67.6% versus 30.4% of patients completing 6 months with no flare and 56.9% versus 28.3% completing 12 months with no flare. Overall corticosteroid use was substantially lower in the pimecrolimus group: 63.7% versus 34.8% of patients did not use corticosteroids at all during the study. Pimecrolimus was also more effective than control treatment in the long-term control of pruritus and the signs of AD. There were no clinically significant differences in incidence of adverse events between the 2 treatment groups. CONCLUSIONS: Treatment with pimecrolimus of early signs and symptoms significantly modified the disease course in infants by reducing the incidence of flares and improving overall control of AD. Pimecrolimus was safe and well tolerated.     

Expression of vascular adhesion protein-1 in atopic eczema

BACKGROUND: Vascular adhesion protein-1 (VAP-1) is an adhesion molecule with an enzymatic activity which partakes in the migration process of lymphocytes. The aim of this study was to investigate VAP-1 expression in atopic eczema (AE) in comparison with healthy controls and psoriatic individuals. MATERIAL AND METHODS: Forty adult patients suffering from AE aged between 18 and 56 years were included in the study. The control group consisted of 35 healthy volunteers aged between 19 and 49 years and of 71 psoriatic patients aged between 23 and 89 years. The serum concentration of soluble VAP-1 (sVAP-1) was evaluated by ELISA and VAP-1 expression in the skin by immunohistochemistry. RESULTS: Serum level of sVAP-1 in AE patients before treatment was significantly higher compared with healthy volunteers. Similarly, a higher mean number of VAP-1-positive vessels was found in both lesional and nonlesional atopic skin compared with healthy skin. Treatment of AE resulted in a significant reduction in the serum level of sVAP-1. On the other hand, both the serum level of sVAP-1 and the number of dermal vessels with expression of VAP-1 were significantly lower in AE patients compared with psoriatic individuals. CONCLUSION: This study indicates the important role of VAP-1 in the pathogenesis of chronic inflammatory cutaneous disorders, including AE.     

Inflammatory cell numbers and cytokine expression in atopic dermatitis after topical pimecrolimus treatment

BACKGROUND: In several clinical trials the topical application of pimecrolimus was shown to be effective in the treatment of atopic dermatitis (AD). By targeting calcineurin-dependent signaling pathways, pimecrolimus controls cytokine gene expression. The purpose of this study was to investigate the effect of pimecrolimus on the inflammatory infiltrate and cytokine expression pattern in AD upon topical therapy. METHODS: From 10 patients with acute AD, skin biopsies as well as immunophenotype and cytokine production of peripheral blood mononuclear cells (PBMC) were examined before and 3 weeks after therapy. RESULTS: The clinical improvement was associated with a marked regression of histopathological features. In particular, the density of the inflammatory infiltrate mostly containing lymphocytes and eosinophils declined. By double immunofluorescent staining, a reduced expression of the T helper (Th) 2 cytokines interleukin (IL)-5, IL-10, and IL-13 in both CD4+ and CD8+ T cells was demonstrated after therapy. Pimecrolimus therapy was also associated with a reduced expression of the Th1 cytokine interferon (IFN)-gamma. Interestingly, the numbers of epidermal CD1a+ dendritic cells increased following treatment. In the peripheral blood, a decrease of lymphocytes and eosinophils was noticed, but the distribution of lymphocyte subpopulations and their capacity of cytokine production did not change. CONCLUSIONS: Topical pimecrolimus exhibits anti-inflammatory effects in AD by reducing the inflammatory cell infiltrate and cytokine expression in the dermis.     

Morphology of atopic eczema

The routine examination of skin biopsy specimens embedded in paraffin and strained with hematoxylin-eosin has failed to allow differentiation of atopic eczema from other types of eczematous dermatitis. The use of 1-μm plastic-embedded sections permits the recognition of in filtrating cell types and blood vessel alterations, thus allowing a refined method to examine cutaneous lesions and permit better definition of cutaneous structures than can be achieved in routinely-processed specimens.
Acute vesicular lesions exhibited marked epidermal intercellular edema (spongiosis) and a dermal inflammatory infiltrate of lymphocytes, and activated lymphocytes with normal numbers of mast cells that exhibited various degrees of hypogranulation. Only rare eosinophils, neutrophils, and basophils were noted. Venular alterations included endothelial cell hypertrophy without necrosis. In lichenified plaques there was epidermal hyperplasia with a dermal inflammatory infiltrate that included increased numbers of fully granulated mast cells and increased numbers of lymphocytes and monocyte-macrophages. Alterations of venules included marked endothelial cell hypertrophy and basement membrane thickening. Cutaneous nerves exhibited demyelination and fibrosis.
Also, increased numbers of Langerhans' cells have been noted in the epidermis of chronic lesions. Despite the absence of eosinophils, major basic protein has been demonstrated in the dermis by direct immunofluorescence techniques. Studies of lymphocyte subsets have shown increased numbers of CD4 + T lymphocytes.     

Differences in skin-prick and patch-test reactivity are related to the heterogeneity of atopic eczema in infants

Current data indicate an obvious relation between food allergy and atopic eczema in infants. However, diagnostic methods for food allergy need to be supplemented. The objective was to study the relevance of food patch testing in the detection of food allergy in correlation with oral food challenge and skin prick tests in atopic infants. Infants with atopic eczema (n = 113) aged 2–24 months were studied. Each patient was subjected to double-blind, placebo-controlled, or open cow's milk challenge, and skin prick and patch tests. Polysensitization, as judged from skin test results, was common in patients with atopic eczema (79/113). Cow's milk challenge was positive in 54/113 infants; reactions were immediate in 36/54 and delayed in 18/54. Immediate-type reactions were associated with skin prick test positivity and delayed reactions with patch test positivity. Altogether 26% of the cow's milk-allergic infants were detected by patch testing only. Patch testing improved the accuracy of skin testing in the diagnosis of food allergy in infants with atopic eczema, but it needs to be standardized. Polysensitization appears to be more common than generally believed among infants with atopic eczema.