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Effects of Cyclosporine and Dexamethasone in a Mouse Model of Atopic Dermatitis
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The Impact of Pimecrolimus Cream 1% on the Quality of Life of Caregivers of Children in South Africa A. I. Manjra1, P. C. Potter2, M. Kadwa3, S. N. Stein3; 1Westville Hospital, Durban, SOUTH AFRICA, 2UCT Lung Institute, Cape Town, SOUTH AFRICA, 3Novartis, South Africa, Johannesburg, SOUTH AFRICA. RATIONALE: . We assessed the effect of Pimecrolimus on the quality of life of caregivers of South African children with atopic eczema. METHODS: 201 paediatric patients aged 2-12 years with mild to moderate atopic eczema in sensitive skin areas received Pimecrolimus cream twice daily while signs and symptoms of atopic eczema were present, together with emollients and also reactive use of methylprednisolone aceponate as rescue medication in the event of a severe flare. Treatment was applied as required over a 3-month period. The primary outcome measure was the mean percentage change in quality of life of caregivers of children with atopic eczema, as assessed by the validated PIQoL-AD Questionnaire. RESULTS: Treatment with Pimecrolimus significantly improved caregivers’ quality of life, as evidenced by a 9.8% increase in mean QoL score at day 14 (p < 0.001) with a further increase of 5.7% noted at day 90 (p < 0.001). Overall, treatment with Pimecrolimus over a 3-month period resulted in a significant total improvement in mean QoL score for caregivers of 15.9% (p < 0.001). Pimecrolimus cream was well tolerated and was also associated with improvement in signs and symptoms with atopic eczema in children, evidenced by significantly improved median IGA scores as compared to baseline. CONCLUSIONS: Pimecrolimus cream significantly improved quality of life of caregivers of South African children with atopic eczema in addition to being effective and well tolerated. Funding: Novartis: South Africa Effects of Cyclosporine and Dexamethasone in a Mouse Model of Atopic Dermatitis L. Stevens, A. Bowden, M. Morton, J. Tepper, A. Tomkinson; Aerovance, Inc, Berkeley, CA. RATIONALE: This study was designed to develop a mouse model of atopic dermatitis (AD) utilizing the epicutaneous (EC) application of Dermatophagoides pteronyssinus (Der p), a common allergen, and to validate the model using treatment with cyclosporine and dexamethasone, two therapies known to be effective in the human disease. METHODS: A patch saturated with Der p was applied to the shaved dorsum of the mice for 4 days on 2 occasions separated by 17 days. Twentyfour hours after removal of the second patch, animals were euthanized, blood collected, and skin biopsies performed for histological and immunohistochemical analysis. The study compared the therapeutic effects of dexamethasone (3 mg/kg) and cyclosporine (50 mg/kg), administered i.p. daily for 7 days, starting 2 days prior to the second patch application. RESULTS: The model demonstrated many of the characteristics associated with the human disease including elevated serum IgE levels, epidermal thickening, and dermal inflammation consisting of CD41 lymphocytes, mast cells, neutrophils and eosinophils. Both cyclosporine and dexamethasone were effective in reducing the severity of the Der p induced epidermal lesion (p 5 0.03 and p 5 0.004, respectively) and dermal inflammation (p 5 0.03 and p 5 0.009, respectively). Neither drug reduced total or Der p specific IgE. Both drugs significantly reduced CD41 T-cells. CONCLUSIONS: Exposure of mice to Der p produces characteristics typically associated with human AD making this model useful for studying the pathophysiology of the disease. The ability of cyclosporine and dexamethasone to reduce the severity of the allergen-induced skin response demonstrates the utility of the model for the assessment of therapeutic agents. Funding: Aerovance, Inc
Maternal Factors Associated with the Development of Infantile Eczema in the First 7 Months of Life S. Suzuki, M. Nakaya, N. Shimojo, Y. Morita, M. Kawada, T. Katsuki, Y. Kohno; Graduate School of Medicine and School of Medicine, Chiba University, Chiba, JAPAN. RATIONALE: The purpose of this prospective study was to investigate several prenatal maternal factors that predict infantile eczema occurring in the first 7 months of life. METHODS: We followed 132 mothers and their infants participating in this study at birth, when maternal information was obtained by questionnaire. The main outcome measure was maternal report of a doctor’s diagnosis of infantile eczema or skin symptoms compatible to infantile eczema persisting over 2 months in the first 7 months of life. We used multiple logistic regression models to assess the associations between several simultaneous predictors and incidence of infantile eczema. RESULTS: Cumulative incidence of infantile eczema in the first 7 months of life was 21.9%. Infants born to mothers with a history of eczema had an adjusted odds ratio (OR) of 4.05 (95% confidence interval [CI]: 1.30, 12.67). Mothers fed with formula in infancy (OR 1.90, 95% CI: 1.11, 3.26), those who perceived lower stress levels before pregnancy (OR 2.06, 95% CI: 1.15, 3.70), and those who had a lower frequency of bowel movement (OR 1.98, 95% CI: 1.01, 3.91) were other predictors. Several other prenatal factors such as exercising, hours of sleep, and diet were not related to risk of infantile eczema. CONCLUSIONS: These findings suggest that influences of prenatal maternal factors as well as maternal genetic predisposition are important in the early presentation of this condition. Funding: Chiba University
Rituximab Therapy Improves Atopic Eczema D. Simon1, S. Ho¨sli2, G. Kostylina2, N. Yawalkar1, H. U. 2 1 Simon ; Dept. of Dermatology, University of Bern, Bern, SWITZERLAND, 2Dept. of Pharmacology, University of Bern, Bern, SWITZERLAND. RATIONALE: Atopic eczema (AE) is a chronic inflammatory skin disorder characterized by eczematous skin lesions, pruritus and typical histopathological features. Although T cells play a key role, B cells are also found in the dermal infiltrate. In 80% of AE patients, elevated total and specific IgE levels can be detected. This study aimed to investigate the effect of a monoclonal anti-CD20 antibody therapy (rituximab) in AE. METHODS: Six patients (2 males; mean age 39 6 7 years) with severe AE received two applications of rituximab, each 1000 mg IV two weeks apart. To evaluate the efficacy of rituximab, we monitored clinical parameters (EASI, pruritus), total and specific IgE levels, and skin histology. Inflammatory cells and cytokine expression in skin lesions were assessed by immunofluorescence analysis before and after therapy. RESULTS: All patients showed an improvement of their skin symptoms within 4 to 8 weeks. The EASI significantly decreased (before therapy: 29.4 6 4.3; week 8: 8.4 6 3.6; p < 0.001). B cells were undetectable in the peripheral blood within 3 days. In contrast, IgE levels did not significantly change as a consequence of rituximab treatment. However, histological alterations, such as spongiosis, acanthosis, and dermal infiltrate, dramatically improved. B cell and T cell numbers were reduced by 50% in the skin. Skin cytokine expression, in particular of IL-13, also declined. CONCLUSIONS: Treatment with rituximab reduces skin inflammation in AE resulting in clinical improvement. Funding: SNF
SATURDAY
Abstracts S35
J ALLERGY CLIN IMMUNOL VOLUME 121, NUMBER 2
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The Impact of Pimecrolimus Cream 1% on the Quality of Life of Caregivers of Children in South Africa A. I. Manjra1, P. C. Potter2, M. Kadwa3, S. N. Stein3; 1Westville Hospital, Durban, SOUTH AFRICA, 2UCT Lung Institute, Cape Town, SOUTH AFRICA, 3Novartis, South Africa, Johannesburg, SOUTH AFRICA. RATIONALE: . We assessed the effect of Pimecrolimus on the quality of life of caregivers of South African children with atopic eczema. METHODS: 201 paediatric patients aged 2-12 years with mild to moderate atopic eczema in sensitive skin areas received Pimecrolimus cream twice daily while signs and symptoms of atopic eczema were present, together with emollients and also reactive use of methylprednisolone aceponate as rescue medication in the event of a severe flare. Treatment was applied as required over a 3-month period. The primary outcome measure was the mean percentage change in quality of life of caregivers of children with atopic eczema, as assessed by the validated PIQoL-AD Questionnaire. RESULTS: Treatment with Pimecrolimus significantly improved caregivers’ quality of life, as evidenced by a 9.8% increase in mean QoL score at day 14 (p < 0.001) with a further increase of 5.7% noted at day 90 (p < 0.001). Overall, treatment with Pimecrolimus over a 3-month period resulted in a significant total improvement in mean QoL score for caregivers of 15.9% (p < 0.001). Pimecrolimus cream was well tolerated and was also associated with improvement in signs and symptoms with atopic eczema in children, evidenced by significantly improved median IGA scores as compared to baseline. CONCLUSIONS: Pimecrolimus cream significantly improved quality of life of caregivers of South African children with atopic eczema in addition to being effective and well tolerated. Funding: Novartis: South Africa Effects of Cyclosporine and Dexamethasone in a Mouse Model of Atopic Dermatitis L. Stevens, A. Bowden, M. Morton, J. Tepper, A. Tomkinson; Aerovance, Inc, Berkeley, CA. RATIONALE: This study was designed to develop a mouse model of atopic dermatitis (AD) utilizing the epicutaneous (EC) application of Dermatophagoides pteronyssinus (Der p), a common allergen, and to validate the model using treatment with cyclosporine and dexamethasone, two therapies known to be effective in the human disease. METHODS: A patch saturated with Der p was applied to the shaved dorsum of the mice for 4 days on 2 occasions separated by 17 days. Twentyfour hours after removal of the second patch, animals were euthanized, blood collected, and skin biopsies performed for histological and immunohistochemical analysis. The study compared the therapeutic effects of dexamethasone (3 mg/kg) and cyclosporine (50 mg/kg), administered i.p. daily for 7 days, starting 2 days prior to the second patch application. RESULTS: The model demonstrated many of the characteristics associated with the human disease including elevated serum IgE levels, epidermal thickening, and dermal inflammation consisting of CD41 lymphocytes, mast cells, neutrophils and eosinophils. Both cyclosporine and dexamethasone were effective in reducing the severity of the Der p induced epidermal lesion (p 5 0.03 and p 5 0.004, respectively) and dermal inflammation (p 5 0.03 and p 5 0.009, respectively). Neither drug reduced total or Der p specific IgE. Both drugs significantly reduced CD41 T-cells. CONCLUSIONS: Exposure of mice to Der p produces characteristics typically associated with human AD making this model useful for studying the pathophysiology of the disease. The ability of cyclosporine and dexamethasone to reduce the severity of the allergen-induced skin response demonstrates the utility of the model for the assessment of therapeutic agents. Funding: Aerovance, Inc
Maternal Factors Associated with the Development of Infantile Eczema in the First 7 Months of Life S. Suzuki, M. Nakaya, N. Shimojo, Y. Morita, M. Kawada, T. Katsuki, Y. Kohno; Graduate School of Medicine and School of Medicine, Chiba University, Chiba, JAPAN. RATIONALE: The purpose of this prospective study was to investigate several prenatal maternal factors that predict infantile eczema occurring in the first 7 months of life. METHODS: We followed 132 mothers and their infants participating in this study at birth, when maternal information was obtained by questionnaire. The main outcome measure was maternal report of a doctor’s diagnosis of infantile eczema or skin symptoms compatible to infantile eczema persisting over 2 months in the first 7 months of life. We used multiple logistic regression models to assess the associations between several simultaneous predictors and incidence of infantile eczema. RESULTS: Cumulative incidence of infantile eczema in the first 7 months of life was 21.9%. Infants born to mothers with a history of eczema had an adjusted odds ratio (OR) of 4.05 (95% confidence interval [CI]: 1.30, 12.67). Mothers fed with formula in infancy (OR 1.90, 95% CI: 1.11, 3.26), those who perceived lower stress levels before pregnancy (OR 2.06, 95% CI: 1.15, 3.70), and those who had a lower frequency of bowel movement (OR 1.98, 95% CI: 1.01, 3.91) were other predictors. Several other prenatal factors such as exercising, hours of sleep, and diet were not related to risk of infantile eczema. CONCLUSIONS: These findings suggest that influences of prenatal maternal factors as well as maternal genetic predisposition are important in the early presentation of this condition. Funding: Chiba University
Rituximab Therapy Improves Atopic Eczema D. Simon1, S. Ho¨sli2, G. Kostylina2, N. Yawalkar1, H. U. 2 1 Simon ; Dept. of Dermatology, University of Bern, Bern, SWITZERLAND, 2Dept. of Pharmacology, University of Bern, Bern, SWITZERLAND. RATIONALE: Atopic eczema (AE) is a chronic inflammatory skin disorder characterized by eczematous skin lesions, pruritus and typical histopathological features. Although T cells play a key role, B cells are also found in the dermal infiltrate. In 80% of AE patients, elevated total and specific IgE levels can be detected. This study aimed to investigate the effect of a monoclonal anti-CD20 antibody therapy (rituximab) in AE. METHODS: Six patients (2 males; mean age 39 6 7 years) with severe AE received two applications of rituximab, each 1000 mg IV two weeks apart. To evaluate the efficacy of rituximab, we monitored clinical parameters (EASI, pruritus), total and specific IgE levels, and skin histology. Inflammatory cells and cytokine expression in skin lesions were assessed by immunofluorescence analysis before and after therapy. RESULTS: All patients showed an improvement of their skin symptoms within 4 to 8 weeks. The EASI significantly decreased (before therapy: 29.4 6 4.3; week 8: 8.4 6 3.6; p < 0.001). B cells were undetectable in the peripheral blood within 3 days. In contrast, IgE levels did not significantly change as a consequence of rituximab treatment. However, histological alterations, such as spongiosis, acanthosis, and dermal infiltrate, dramatically improved. B cell and T cell numbers were reduced by 50% in the skin. Skin cytokine expression, in particular of IL-13, also declined. CONCLUSIONS: Treatment with rituximab reduces skin inflammation in AE resulting in clinical improvement. Funding: SNF
SATURDAY
Abstracts S35
J ALLERGY CLIN IMMUNOL VOLUME 121, NUMBER 2