Effects of pimecrolimus compared with triamcinolone acetonide cream on skin barrier structure in atopic dermatitis: a randomized, double-blind, right-left arm trial.

Patients with atopic dermatitis (AD) have an epidermal barrier dysfunction, which allows invasion of allergens to occur. Stratum corneum skin barrier is formed by corneocytes and extracellular lipids extruded from the epidermal lamellar bodies. In a controlled, randomized, double-blinded, right-left comparison study we investigated the effect of pimecrolimus (PIM) cream compared with triamcinolone acetonide cream (TA) on the skin barrier in 15 patients with symmetrical elbow lesions of AD. In punch biopsies, before and after treatment, skin lipid bilayer and lamellar body structure were examined by transmission electron microscopy (TEM). Partial Eczema Area and Severity Index (pEASi), stratum corneum hydration, and transepidermal water loss (TEWL) were monitored on days 1, 8 and 22. The pEASi was significantly more improved with TA compared with PIM, whereas stratum corneum hydration was slightly more improved after treatment with PIM. The TEM revealed a strong reduction in lamellar bodies in lesional skin of AD; only 32% of the lamellar bodies were normal. A significantly higher number of normal lamellar bodies was found after 3 weeks of treatment with PIM (58%; p < 0.005). An increase in lamellar bodies also occurred with TA treatment (46%; p < 0.05); however, significantly less than with PIM (p < 0.05). Clinical score and TEWL were more improved after treatment with TA, whereas the lamellar bodies were more normal after treatment with PIM.

Development of a physiologically based computational kidney model to describe the renal excretion of hydrophilic agents in rats.

A physiologically based kidney model was developed to analyze the renal excretion and kidney exposure of hydrophilic agents, in particular contrast media, in rats. In order to study the influence of osmolality and viscosity changes, the model mechanistically represents urine concentration by water reabsorption in different segments of kidney tubules and viscosity dependent tubular fluid flow. The model was established using experimental data on the physiological steady state without administration of any contrast media or drugs. These data included the sodium and urea concentration gradient along the cortico-medullary axis, water reabsorption, urine flow, and sodium as well as urea urine concentrations for a normal hydration state. The model was evaluated by predicting the effects of mannitol and contrast media administration and comparing to experimental data on cortico-medullary concentration gradients, urine flow, urine viscosity, hydrostatic tubular pressures and single nephron glomerular filtration rate. Finally the model was used to analyze and compare typical examples of ionic and non-ionic monomeric as well as non-ionic dimeric contrast media with respect to their osmolality and viscosity. With the computational kidney model, urine flow depended mainly on osmolality, while osmolality and viscosity were important determinants for tubular hydrostatic pressure and kidney exposure. The low diuretic effect of dimeric contrast media in combination with their high intrinsic viscosity resulted in a high viscosity within the tubular fluid. In comparison to monomeric contrast media, this led to a higher increase in tubular pressure, to a reduction in glomerular filtration rate and tubular flow and to an increase in kidney exposure. The presented kidney model can be implemented into whole body physiologically based pharmacokinetic models and extended in order to simulate the renal excretion of lipophilic drugs which may also undergo active secretion and reabsorption.

Cost-intensive, time-consuming, problematical? How physicians in private practice experience the care of urticaria patients.

BACKGROUND: Urticaria is a common and frequently debilitating disease. Nevertheless, there are only few studies examining the situation of urticaria patient care. PATIENTS AND METHODS: In this cross-sectional study, we surveyed dermatologists, pediatricians and general practitioners in the practice setting regarding the epidemiology, situation of care as well as the perception of their patients with chronic spontaneous urticaria. RESULTS: 776 data sets were available. The results show a high frequency of consultations due to chronic spontaneous urticaria. Most of the patients were reported to suffer moderately to severely and to have had history of disease of well over one year. The pediatricians indicated fewer diseases and shorter courses. The majority of participants stated that the time and cost spent on care, as well as the frequency of follow-up visits, are above average. In addition, chronic spontaneous urticaria patients were reported to be a group with a strong emotional burden and high expectations as well as a group that is difficult to satisfy and hard to guide. Only a small minority of physicians rated patient satisfaction with current treatment options and therapy success as high. CONCLUSIONS: Chronic spontaneous urticaria plays an important role in daily practice. Problems are reported on various areas of care. Resolving these problems presents a major challenge and is crucial for improving the quality of patient care.

Evaluation of the atrophogenic potential of hydrocortisone 1% cream and pimecrolimus 1% cream in uninvolved forehead skin of patients with atopic dermatitis using optical coherence tomography.

Topical corticosteroids are widely used to treat atopic dermatitis (AD), but their anti-inflammatory mode of action can be accompanied by several unwanted side effects including skin atrophy and telangiectasia. In this 8-week, investigator-blinded, intraindividual right-left comparison study with patients with mild-to-moderate AD, hydrocortisone 1% cream (HCT) was applied twice daily for 4 weeks on one side of forehead skin without clinical signs of AD and pimecrolimus 1% cream (PIM) on the other. Epidermal and dermal thickness were assessed by optical coherence tomography (OCT) and high-frequency ultrasound, respectively. Skin atrophy and telangiectasia were assessed by contact dermatoscopic photography (Dermaphot(®)). Treatment with HCT leads to a significant decrease in epidermal thickness after only 2 weeks of treatment, while the decrease in PIM-treated sites was less pronounced and was not statistically significant. By 4 weeks after the end of treatment, epidermal thickness returned to baseline values. No dermal thinning or development of telangiectasia could be observed by means of ultrasound or Dermaphot(®), respectively. In summary, this study indicates that a 2-week single course of topical treatment with a mildly potent steroid can cause transient epidermal thinning, an effect not seen in the PIM group. The slight decrease with PIM - although not significant - could be due to normalization of the increased skin thickness caused by a subclinical inflammation in AD. This study suggests that PIM may be safer for treatment of AD in sensitive skin areas like the face, especially when repeated application is required.

Efficacy and safety of omalizumab in patients with chronic urticaria who exhibit IgE against thyroperoxidase.

BACKGROUND: A subgroup of patients with chronic spontaneous urticaria (CU) exhibits IgE antibodies directed against autoantigens, such as thyroperoxidase (TPO). We conducted this study to investigate whether such patients with CU with IgE against TPO benefit from treatment with omalizumab, a humanized anti-IgE mAb licensed for the treatment of severe persistent allergic (IgE-mediated) asthma. OBJECTIVES: We sought to assess the efficacy of omalizumab treatment in patients with CU with IgE autoantibodies against TPO. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study patients with CU (male/female, 18-70 years of age) with IgE autoantibodies against TPO who had persistent symptoms (wheals and pruritus) despite standard antihistamine therapy were randomized to receive either omalizumab (75-375 mg, dose determined by using the approved asthma dosing table) or placebo subcutaneously once every 2 or 4 weeks for 24 weeks. The primary end point was the change from baseline in mean weekly urticaria activity score after 24 weeks of treatment, as calculated from patients' diaries. The safety and tolerability of omalizumab were also assessed. RESULTS: Of the 49 randomized patients (omalizumab, n = 27; placebo, n = 22), 42 completed the study. At week 24, patients demonstrated a mean reduction in the weekly urticaria activity score from baseline of 17.8 with omalizumab and 7.9 with placebo (P = .0089). Complete protection from wheal development was observed in 19 (70.4%) patients in the omalizumab group compared with only 1 (4.5%) patient in the placebo group. The rate of adverse events was similar in both groups. CONCLUSIONS: The results of this study indicate that omalizumab is an effective treatment option for patients with CU with IgE autoantibodies against TPO who are refractory to conventional treatment.

Differential suppression of epidermal antimicrobial protein expression in atopic dermatitis and in EFAD mice by pimecrolimus compared to corticosteroids.

It has been suggested that the increased rate of bacterial infection in atopic dermatitis (AD) may be caused by reduced antimicrobial protein (AMP) expression. We were interested whether common treatments in AD affect antimicrobial defense. We investigated the effects of topically applied corticosteroids betamethasone valerate (BV) and triamacinolone acetonide (TA) and those of the calcineurin inhibitor pimecrolimus for 3 weeks on AMP expression in AD. BV and TA treatment in AD led to a significant reduction in AMP expression; protein expression of human beta-defensins (hBD)-2 and hBD-3, psoriasin, RNase 7 and cathelicidin LL-37 was below the level in skin of healthy controls. After pimecrolimus treatment, AMP expression was also reduced but less compared to BV and TA; the expression levels of hBD-2, psoriasin and RNase 7 still remained above the control levels. In essential fatty acid-deficient (EFAD) mice, a model of chronic skin barrier disease with inflammation, expression of the mouse beta-defensins mBD-1, mBD-3 and mBD-14 (orthologues for hBD-1, hBD-2 and hBD-3, respectively), was reduced by both treatments, again more pronounced by BV compared to pimecrolimus. In summary, we found that treatment for AD with corticosteroids in human skin and EFAD mice caused a strong reduction in AMPs; reduction was less with pimecrolimus. This result may explain the clinical observation that prolonged treatment with topical corticosteroids sometimes leads to bacterial infection.

Safety of a depigmented, polymerized vaccine for the treatment of allergic rhinoconjunctivitis and allergic asthma.

BACKGROUND: Clinical efficacy of specific immunotherapy (SIT) with depigmented, polymerized allergen extracts is well documented in placebo-controlled trials, and safety data are encouraging although further data are required. METHODS: We enrolled 768 patients (51% men; mean age, 31 years) in this prospective multicenter study on safety and clinical effects of Depigoid (Laboratorios LETI, S.L., Madrid, Spain). Immunotherapy consisted of four injections of increasing doses of Depigoid at weekly intervals followed by monthly maintenance injections. All adverse events were documented. Moreover, nose, eye, and lung symptoms were assessed at baseline after 3 and 6 months. Results were compared with the scores of the preceding season. RESULTS: Rates for local and systemic reactions that might possibly be related to the study medication were 2.36 and 4.56/1000 injections, respectively. With 5923 injections given, 14 local reactions were reported (5 patients), and 27 systemic reactions were reported, including 20 of grade 1 (6 patients) and 7 of grade 2 (4 patients). The best safety profile was seen for patients vaccinated against house-dust mites. Reductions in nose, eye, and lung symptoms as well as in concomitant medication compared with either the preceding season (pollen-sensitized patients) or the baseline (house-dust mite-sensitized patients) were observed at the end of study. CONCLUSION: In this large multicenter study on 768 patients with allergic rhinoconjunctivitis and allergic asthma under daily practice conditions SIT with Depigoid was well tolerated with low rates of local and systemic reactions. Furthermore, SIT resulted in considerable reductions in symptoms and concomitant medication.

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

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.

Role of the epidermal barrier in atopic dermatitis.

The skin's permeability barrier protects against extensive water loss and prevents the entry into the skin of harmful substances like irritants, allergens and microorganisms. The permeability barrier is mainly located in the stratum corneum and consists of corneocytes and a lipid-enriched intercellular domain. The barrier is formed during epidermal differentiation. In atopic dermatitis the skin barrier is disturbed already in non-lesional skin. The disturbed skin barrier allows the entry of environmental allergens from house dust mites, animal dander and grass pollen into the skin. In predisposed individuals these allergens may trigger via immunologic pathways the inflammation of atopy. The causes for the disturbed epidermal skin barrier are changes in skin lipids and in epidermal differentiation, in particular filaggrin mutations. Filaggrin mutations lead to a disturbed skin barrier and dry skin which are hallmarks in atopic dermatitis. Therapeutic agents influence the skin barrier differently; topical therapy with potent corticosteroids does not lead to the repair of the barrier in atopic dermatitis, whereas therapy with the calcineurin inhibitors and lipid-containing emulsions support barrier repair.

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

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.

Skin physiological parameters confirm the therapeutic efficacy of pimecrolimus cream 1% in patients with mild-to-moderate atopic dermatitis.

In this double-blind, within-patient vehicle-controlled study, patients with mild-to-moderate atopic dermatitis (AD) were treated for 3 weeks twice daily with pimecrolimus cream 1% on one forearm and with vehicle cream on the other forearm. Efficacy of treatment was assessed clinically using the Atopic Dermatitis Severity Index (ADSI), the Investigators Global Assessment (IGA) and the pruritus visual analogue scale. In parallel, blood microcirculation in the skin was measured as an objective parameter for skin inflammation. Skin hydration and transepidermal water loss (TEWL) were monitored as parameter relevant for the barrier function. Treatment with pimecrolimus cream 1% resulted in a quick and marked improvement of signs and symptoms of AD and a significant reduction of microcirculation from 33.90 to 15.55 AU (P < 0.0001). Skin hydration increased continually from 42.86 to 52.69 AU (P = 0.002) and TEWL decreased from 35.30 to 21.50 g/m(2)/h (P = 0.001), indicating restoration of skin barrier. At vehicle-treated sites changes of skin physiological parameters were less pronounced and observed only initially with later plateau or even reversal. At the end of the study, there were significant differences for all measured skin physiological parameters between pimecrolimus cream 1% and vehicle: microcirculation 12.15 AU (P = 0.004), skin hydration 7.12 AU (P = 0.002), TEWL 11.38 g/m(2)/h (P = 0.004). Non-invasive evaluation of microcirculation and barrier functionality thus represent a valuable tool for the objective assessment of treatment response to pimecrolimus cream 1%.

StabiEL: stabilization of skin condition with Elidel--a patients' satisfaction observational study addressing the treatment, with pimecrolimus cream, of atopic dermatitis pretreated with topical corticosteroid.

BACKGROUND: The objective of this 4-month multicentre observational study was to evaluate safety and efficacy of intermittent long-term treatment of patients with atopic dermatitis (AD) with pimecrolimus cream 1% in the daily practice and to compare it with the preceding topical corticosteroid-based therapy in retrospective. PATIENTS AND METHODS: Overall severity of AD and individual symptoms were assessed in 3200 patients by the physician, whereas acceptance of treatment and satisfaction of patients was investigated using a patient questionnaire. RESULTS: The percentage of patients clear or almost clear of symptoms increased from 12% to 82%. Seventy-four per cent of physician rated the treatment better than the preceding therapy, and 21% noted no difference. Seventy-seven per cent of the patients asserted that long-term intermittent treatment with pimecrolimus reduces the frequency of flares as opposed to less than 27% for topical corticosteroids. Patients also felt that pimecrolimus results in a higher improvement in quality of life; 84% stated that pimecrolimus stabilized the skin compared with 27% for topical steroids. CONCLUSION: Intermittent treatment of AD patients with pimecrolimus cream 1% is effective and well tolerated, and results in higher patient satisfaction compared with topical corticosteroids in retrospective.

A randomized, double-blind, vehicle-controlled study of 1% pimecrolimus cream in adult patients with perioral dermatitis.

BACKGROUND: Perioral dermatitis (POD) is a common dermatosis without standard therapy. OBJECTIVE: We sought to evaluate pimecrolimus cream 1% in POD. METHODS: We conducted a multicenter, randomized, double-blind, parallel-group study in adult patients with POD treated twice daily with pimecrolimus cream 1% or vehicle until clearance for up to 4 weeks. Follow-up took place 4 and 8 weeks after treatment. RESULTS: Patients treated with pimecrolimus had an average POD Severity Index score of 2.6 compared with 3.5 for patients treated with vehicle. Both groups had baseline scores of 5.2. The between-group difference was 0.9 (95% confidence level 0.4, 1.4, P = .0011). Patients with history of topical corticosteroids benefited most. Pimecrolimus-treated patients reported greater improvement in quality of life. There were no group differences regarding safety. LIMITATIONS: Pimecrolimus vehicle is not a true placebo. CONCLUSIONS: Pimecrolimus rapidly improves clinical symptoms and quality of life of patients with POD, being most effective in corticosteroid-induced POD.

Safety and efficacy of pimecrolimus cream 1% in the daily practice: results of a patient self-observation study in patients with atopic dermatitis.

BACKGROUND: Pimecrolimus cream 1% has proven to be well-tolerated and effective in controlled clinical studies in patients with atopic dermatitis (AD). In a 15-week patient self-observation study, safety and efficacy was investigated in the daily practice. PATIENTS AND METHODS: 3502 patients with AD (mean age 26.2 +/- 18 years, 62% female) received pimecrolimus cream 1% from 810 physicians in the German Federal Republic. The severity of the disease was assessed at baseline, two times during the 15-week observation period and at the end of treatment. Patients recorded daily the degree of erythema and pruritus. At the end of treatment, safety and efficacy were assessed by the physician based on patient's daily records and by the patient. RESULTS: The percentage of patients with severe or massive AD decreased from 25% to 7%, whereas the percentage of patients without or with mild symptoms increased from 9% to 55%.The efficacy of treatment was rated by physicians as good or very good in 83.5% of cases and by 79% of patients. At baseline 35% of the patients were free of flares as compared to 75% at the end of therapy. Disease control was better in patients who followed the recommended treatment algorithm for pimecrolimus cream. Tolerability was mostly rated as good or very good. CONCLUSION: Treatment with pimecrolimus cream 1% for patients with AD is well-tolerated and effective in daily practice.

Steroid-sparing effect of pimecrolimus cream 1% in children with severe atopic dermatitis.

OBJECTIVE: To investigate if pimecrolimus cream 1% reduces the need for steroids in the long-term management of severe pediatric atopic dermatitis (AD). METHODS: A total of 184 pediatric patients (aged 2-17 years) with a history of severe AD according to Rajka and Langeland were enrolled. Patients were randomized to treatment with pimecrolimus cream or vehicle cream for a 24-week period. Prednicarbate 0.25% was applied as rescue medication. RESULTS: Patients on pimecrolimus required steroids on a mean of 29% of study days, compared with 35% of patients on vehicle (p = 0.1841). On the head and neck only, the respective figures were 10 versus 19% (p = 0.0009). In patients enrolled with acute severe disease (Investigator's Global Assessment > or = 4), steroids were used on 28% of the days in the pimecrolimus group compared to 45% in the control group (p = 0.0024). On the head and neck, steroids were used on 10% of study days with pimecrolimus versus 30% with vehicle (p < 0.0001). CONCLUSION: The results indicate that the need for topical steroids on the head and neck is reduced with pimecrolimus cream 1% in the management of severe pediatric AD according to the definition of Rajka and Langeland.

1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of intertriginous psoriasis: a double-blind, randomized controlled study.

OBJECTIVE: During the last decades, management of intertriginous psoriasis (IP) has been unsatisfactory because of the adverse effects associated with long-term corticosteroid application and the lack of alternatives. Recently, both pimecrolimus and tacrolimus have been investigated for this indication and shown to be safe and effective. So far, to our knowledge, a comparison of one of these drugs with standard regimens for IP has not been performed. DESIGN: A single-center, 4-week, double-blind, randomized, vehicle-controlled comparison study to assess the safety and efficacy of 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone valerate in the treatment of IP. SETTING: Dermatologic hospital at Ruhr University of Bochum. PATIENTS: Eighty adults with IP. INTERVENTIONS: Treatment of IP with 1% pimecrolimus, 0.005% calcipotriol, 0.1% betamethasone, or the vehicle once daily for 28 days. MAIN OUTCOME MEASURES: Mean reduction of the Modified Psoriasis Area and Severity Index (M-PASI) score after 28 days of treatment was considered the primary outcome measure, which was analyzed on an intention-to-treat basis. The secondary outcome was a visual analog scale score for itching. RESULTS: After 4 weeks of treatment, the 3 active compounds and the vehicle resulted in a significant decrease in mean M-PASI score (86.4% for 0.1% betamethasone, 62.4% for 0.005% calcipotriol, 39.7% for 1% pimecrolimus, and 21.1% for vehicle). The 0.1% betamethasone was significantly more effective than 1% pimecrolimus during the study period (P<.05). No significant difference was found between 0.005% calcipotriol and 0.1% betamethasone and between 0.005% calcipotriol and 1% pimecrolimus. The visual analog scale score for pruritus decreased by 78% for 0.1% betamethasone, 57% for 0.005% calcipotriol, 35% for 1% pimecrolimus, and 43% for the vehicle, again demonstrating a clear advantage for the corticosteroid (P<.05). CONCLUSIONS: The 1% pimecrolimus was shown to be less potent than 0.1% betamethasone in the treatment of IP. Considering the adverse-effect profile of long-term application of corticosteroids, occasional or intermittent rescue therapy with short-term topical corticosteroids and maintenance with a less potent agent, such as 1% pimecrolimus or 0.005% calcipotriol, might be appropriate for patients with IP in general practice.

Treatment of infants with atopic eczema with pimecrolimus cream 1% improves parents' quality of life: a multicenter, randomized trial.

Atopic eczema begins primarily in infancy or early childhood, and sleep loss due to night-time pruritus can have a considerable impact on patients' and parents' quality of life (QoL). In this study, infants (n = 196) with mild to severe atopic eczema were randomized 2:1, double-blind, to receive either pimecrolimus cream 1% (Elidel, Novartis Pharma, Nürnberg, Germany) or the corresponding vehicle bid for 4 wk, followed by a 12 wk, open-label phase and a 4 wk, treatment-free, follow-up period. The parents' QoL was measured at baseline and at the end of the double-blind phase, using the questionnaire 'QoL in Parents of Children with Atopic Dermatitis' (PQoL-AD), thus data presented here refer to the initial 4-wk treatment phase only. After 4 wk of double-blind treatment, an increase in the mean percentage change from baseline in eczema area and severity index of 71.5% was observed with pimecrolimus, compared with 19.4% with vehicle. The increase in efficacy was paralleled by the following mean percentage changes from baseline in the five domains of the questionnaire in pimecrolimus and vehicle, respectively: psychosomatic well-being: 14.6% vs. 6.2%; effects on social life: 6.7% vs. 2.3%; confidence in medical treatment: 10.0% vs. 3.7%; emotional coping: 16.1% vs. 6.5%; acceptance of disease: 19.6% vs. 7.0%. Analysis (ancova) of the dependent variable difference from baseline and the covariate baseline value revealed values of p < 0.05 for all five domains, despite the very short duration of the study. It is concluded that improvements in atopic eczema in infants achieved by treatment with pimecrolimus have a significant beneficial effect on the QoL of parents.