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CU-QoL: A new specific quality of life questionnaire for patients with chronic urticaria
S178 Abstracts
709
Chronic Urticaria: Association With Celiac Disease
G. B. Pajno, G. Magazzù, L. Caminiti, C. Sferlazzas, D. Vita, G. Barberio; Department of Pediatrics - Allergy Unit, Istituto Clinica Pediatrica, Messina, ITALY. RATIONALE: Recent advances driven by serological assays have led to the realization that clinically overt cases of Celiac Disease (CD) represent only a small proportion of patients with the disorder. In addition to the classic and the atypical forms of celiac disease, silent and latent forms have been described. Chronic Urticaria (CU), conventionally defined as the occurrence of daily or almost daily wheals with or without accompanying angiodema for at least 6 weeks, is a frustrating illness for patients as well as physicians since the aetiology is often no determined. METHODS: Eighty two patients (age range 1-22 years) were recruited provided that they met the diagnostic criteria for CU. Two-thousands and forty-five school children (age range 7-10 years), without urticaria undergone a screening for CD as controls. RESULTS: Out of 82 patients, four children (4.8%; 95% CI 1-12%) and 17 out of 2545 (0.67%; 95% CI 0-1%) controls resulted as having CD (OR 7.7; 95% CI 2.3-23.2; p=0.0003). All were TGA and EMA positive and diagnosis of CD was confirmed by a 3a-3c degree of villous atrophy. All 4 children were placed on gluten free diet (GFD) with complete resolution of their hives, they were able to discontinue H1 antihistamines, H2 antihistamines and steroids. The symptoms’ improvement preceded the normalization of antiendomisyal (EMA) and antitransglutaminase antibodies (TGA) which disappeared in all patients within 9 months. CONCLUSIONS: Our findings suggest that diagnosis of CD should be considered in children with refractory chronic urticaria, even when no overt symptoms of celiac disease are present. Funding: University of Messina - Italy
CU-QoL: A New Specific Quality of Life Questionnaire for Patients With Chronic Urticaria I. Baiardini1, M. Pasquali1, M. Braga2, C. Lombardi3, F. Fumagalli1, L. Guerra1, E. Compalati1, F. Braido1, G. W. CANONICA1; 1Dept of Internal Medicine Genoa University, Allergy & Respiratory Diseases, Genoa, ITALY, 2Allergy Service, Brescia General Hospital, Brescia, ITALY, 3Dept of Internal Medicine, Pneumoallergology Unit, S Orsola Hospital, Brescia, ITALY. RATIONALE: To date specific instruments aimed at assessing Health Related Quality of Life (HRQoL) in Chronic Urticaria (CU) are not available. Aim of our study was to develop and validate a specific HRQoL questionnaire for adult patients with CU. MATERIALS AND METHODS: In the development procedure of CUQoL an initial questionnaire of 39 items was compiled and given to a first pool of CU 76 patients; then, the 22 most significant items were detected and converted into questions evaluating the answers on a Likert scale of 5 steps. Consequently, this final questionnaire underwent a validation procedure to assess its construct validity, internal consistency, reliability, and responsiveness. 125 patients (44% M, 56% F) were evaluated, (age 53.69 ± 11.7 years). RESULTS: Factor analysis revealed a six-dimensional structure, which explained up 59.97 of the total variance. All the dimensions showed satisfactory Chronbach’s alpha values: Pruritus (0.79), Swelling (0.65) Impact on life activities (0.83), Sleep problems (0.77), Embarrassment (0.83), Limits (0.74). In stable conditions CU-QoL showed a good reliability, with Inter Class Coefficients >58. Responsiveness to clinical changes was accomplished. CONCLUSION: These results provide evidence that CU-QoL has specificity enough for being a valid tool for detecting the relative burden of CU on HRQoL, and for obtaining a global assessment both of CU impact and of treatments for it, taking into account the patient’s point of view. Funding: Genoa University
710
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
Maturing of Monocyte Derived Dentritic Cells in the Presence of Flea Antigen Extracts in Patients With Flea-Bite Induced Papular Urticaria A. Cuéllar1, E. García2, A. Rodríguez1, E. Halpert2, A. Gómez1; 1Pontificia Universidad Javeriana, Bogotá, COLOMBIA, 2Fundación Santafé de Bogotá, Bogotá, COLOMBIA. RATIONALE: Dendritic cells (DC) are stimulated by recognition of antigens. This study evaluated the capacity of a whole flea extract to induce maturing of monocyte derived dentritic cells in patients with fleabite antigen papular urticaria and healthy children. METHODS: Flea extracts were obtained through maceration in PBS and quantification of proteins by the Bradford technique. DCs were obtained of periphereal blood monocytes in the presence of GM-CSF and interleukin 4 (IL-4). At day 5 of culture, flea extract or LPS were added. Surface expression of CD14, CD86, HLA-DR and CD83 were evaluated by flow cytometry. RESULTS: A whole flea extract was obtained with a protein concentration of 1.3 mg/ml. On the 7th day of culture, mature DCs increased HLADR and CD86 expression and expression of CD83 was 66% in patients and 63% in controls. Exposure to a flea antigenic extract shows HLA-DR and CD86 expression similar to the immature DCs expression. The CD83 expression was of 5% in patients and 5.6% in controls. CONCLUSIONS: The results show that there is no difference in the levels of membrane HLA-DR, CD86 or CD83 expression or in the maturing of dentritic cells between healthy children and patients with flea biteinduced papular urticaria when exposed in vitro to flea extracts. Funding: Pontificia Universidad Javeriana
711
MONDAY
Chronic Urticaria Sera Increase Basophil CD203c Surface Expression K. M. Yasnowsky1,2, D. J. Schoen1, P. K. Vedanthan2, R. Alam1, S. C. Dreskin2, R. Harbeck1; 1Allergy and Clinical Immunology, National Jewish Medical and Research Center, Denver, CO, 2Allergy and Clinical Immunology, University of Colorado Health Sciences Center, Denver, CO. RATIONALE: Approximately 40% of patients with chronic urticaria (CU) have antibodies to the high affinity IgE receptor (FcεRI). Patients with auto-antibodies are currently identified by histamine release assay, autologous serum skin testing and Western blot. CD203c is expressed specifically on basophils, mast cells and their CD34+ progenitor cells and is upregulated by cross-linking of FcRI receptors. CD203c may be a useful marker to identify urticaria patients with functional antibodies to the FcRI receptor. METHODS: Sera were obtained from CU patients with positive autologous skin tests and normal controls. Basophils from whole blood were identified by flow cytometry based on the presence of CD203c on high expressing IgE positive cells. Seven normal individuals were screened and one donor was identified based on the marked upregulation in response to fMLP and anti-FcRI antibody. Aliquots of this donor’s whole blood were incubated with sera from 17 CU patients and 10 normal controls. RESULTS: Incubation of donor basophils with sera from CU patients (n=17) demonstrated significant upregulation of CD203c compared to normal sera (n=10). The mean percent of activated basophils compared to buffer background in CU patients sera was 36.6% ± 4.9% (range 2.1% to 64.4%) versus -0.6 %±0.1 % (range -1.2% to 0.0%) in normal controls (p<0.0001). Positive controls fMLP and anti-FcRI antibody were 50.5% and 38.5%, respectively. CONCLUSIONS: Sera from patients with chronic urticaria significantly upregulate basophil CD203c. This in vitro assay may provide an easier method to identify patients with autoimmune urticaria and further our understanding of mechanisms of chronic urticaria.
712
709
Chronic Urticaria: Association With Celiac Disease
G. B. Pajno, G. Magazzù, L. Caminiti, C. Sferlazzas, D. Vita, G. Barberio; Department of Pediatrics - Allergy Unit, Istituto Clinica Pediatrica, Messina, ITALY. RATIONALE: Recent advances driven by serological assays have led to the realization that clinically overt cases of Celiac Disease (CD) represent only a small proportion of patients with the disorder. In addition to the classic and the atypical forms of celiac disease, silent and latent forms have been described. Chronic Urticaria (CU), conventionally defined as the occurrence of daily or almost daily wheals with or without accompanying angiodema for at least 6 weeks, is a frustrating illness for patients as well as physicians since the aetiology is often no determined. METHODS: Eighty two patients (age range 1-22 years) were recruited provided that they met the diagnostic criteria for CU. Two-thousands and forty-five school children (age range 7-10 years), without urticaria undergone a screening for CD as controls. RESULTS: Out of 82 patients, four children (4.8%; 95% CI 1-12%) and 17 out of 2545 (0.67%; 95% CI 0-1%) controls resulted as having CD (OR 7.7; 95% CI 2.3-23.2; p=0.0003). All were TGA and EMA positive and diagnosis of CD was confirmed by a 3a-3c degree of villous atrophy. All 4 children were placed on gluten free diet (GFD) with complete resolution of their hives, they were able to discontinue H1 antihistamines, H2 antihistamines and steroids. The symptoms’ improvement preceded the normalization of antiendomisyal (EMA) and antitransglutaminase antibodies (TGA) which disappeared in all patients within 9 months. CONCLUSIONS: Our findings suggest that diagnosis of CD should be considered in children with refractory chronic urticaria, even when no overt symptoms of celiac disease are present. Funding: University of Messina - Italy
CU-QoL: A New Specific Quality of Life Questionnaire for Patients With Chronic Urticaria I. Baiardini1, M. Pasquali1, M. Braga2, C. Lombardi3, F. Fumagalli1, L. Guerra1, E. Compalati1, F. Braido1, G. W. CANONICA1; 1Dept of Internal Medicine Genoa University, Allergy & Respiratory Diseases, Genoa, ITALY, 2Allergy Service, Brescia General Hospital, Brescia, ITALY, 3Dept of Internal Medicine, Pneumoallergology Unit, S Orsola Hospital, Brescia, ITALY. RATIONALE: To date specific instruments aimed at assessing Health Related Quality of Life (HRQoL) in Chronic Urticaria (CU) are not available. Aim of our study was to develop and validate a specific HRQoL questionnaire for adult patients with CU. MATERIALS AND METHODS: In the development procedure of CUQoL an initial questionnaire of 39 items was compiled and given to a first pool of CU 76 patients; then, the 22 most significant items were detected and converted into questions evaluating the answers on a Likert scale of 5 steps. Consequently, this final questionnaire underwent a validation procedure to assess its construct validity, internal consistency, reliability, and responsiveness. 125 patients (44% M, 56% F) were evaluated, (age 53.69 ± 11.7 years). RESULTS: Factor analysis revealed a six-dimensional structure, which explained up 59.97 of the total variance. All the dimensions showed satisfactory Chronbach’s alpha values: Pruritus (0.79), Swelling (0.65) Impact on life activities (0.83), Sleep problems (0.77), Embarrassment (0.83), Limits (0.74). In stable conditions CU-QoL showed a good reliability, with Inter Class Coefficients >58. Responsiveness to clinical changes was accomplished. CONCLUSION: These results provide evidence that CU-QoL has specificity enough for being a valid tool for detecting the relative burden of CU on HRQoL, and for obtaining a global assessment both of CU impact and of treatments for it, taking into account the patient’s point of view. Funding: Genoa University
710
J ALLERGY CLIN IMMUNOL FEBRUARY 2005
Maturing of Monocyte Derived Dentritic Cells in the Presence of Flea Antigen Extracts in Patients With Flea-Bite Induced Papular Urticaria A. Cuéllar1, E. García2, A. Rodríguez1, E. Halpert2, A. Gómez1; 1Pontificia Universidad Javeriana, Bogotá, COLOMBIA, 2Fundación Santafé de Bogotá, Bogotá, COLOMBIA. RATIONALE: Dendritic cells (DC) are stimulated by recognition of antigens. This study evaluated the capacity of a whole flea extract to induce maturing of monocyte derived dentritic cells in patients with fleabite antigen papular urticaria and healthy children. METHODS: Flea extracts were obtained through maceration in PBS and quantification of proteins by the Bradford technique. DCs were obtained of periphereal blood monocytes in the presence of GM-CSF and interleukin 4 (IL-4). At day 5 of culture, flea extract or LPS were added. Surface expression of CD14, CD86, HLA-DR and CD83 were evaluated by flow cytometry. RESULTS: A whole flea extract was obtained with a protein concentration of 1.3 mg/ml. On the 7th day of culture, mature DCs increased HLADR and CD86 expression and expression of CD83 was 66% in patients and 63% in controls. Exposure to a flea antigenic extract shows HLA-DR and CD86 expression similar to the immature DCs expression. The CD83 expression was of 5% in patients and 5.6% in controls. CONCLUSIONS: The results show that there is no difference in the levels of membrane HLA-DR, CD86 or CD83 expression or in the maturing of dentritic cells between healthy children and patients with flea biteinduced papular urticaria when exposed in vitro to flea extracts. Funding: Pontificia Universidad Javeriana
711
MONDAY
Chronic Urticaria Sera Increase Basophil CD203c Surface Expression K. M. Yasnowsky1,2, D. J. Schoen1, P. K. Vedanthan2, R. Alam1, S. C. Dreskin2, R. Harbeck1; 1Allergy and Clinical Immunology, National Jewish Medical and Research Center, Denver, CO, 2Allergy and Clinical Immunology, University of Colorado Health Sciences Center, Denver, CO. RATIONALE: Approximately 40% of patients with chronic urticaria (CU) have antibodies to the high affinity IgE receptor (FcεRI). Patients with auto-antibodies are currently identified by histamine release assay, autologous serum skin testing and Western blot. CD203c is expressed specifically on basophils, mast cells and their CD34+ progenitor cells and is upregulated by cross-linking of FcRI receptors. CD203c may be a useful marker to identify urticaria patients with functional antibodies to the FcRI receptor. METHODS: Sera were obtained from CU patients with positive autologous skin tests and normal controls. Basophils from whole blood were identified by flow cytometry based on the presence of CD203c on high expressing IgE positive cells. Seven normal individuals were screened and one donor was identified based on the marked upregulation in response to fMLP and anti-FcRI antibody. Aliquots of this donor’s whole blood were incubated with sera from 17 CU patients and 10 normal controls. RESULTS: Incubation of donor basophils with sera from CU patients (n=17) demonstrated significant upregulation of CD203c compared to normal sera (n=10). The mean percent of activated basophils compared to buffer background in CU patients sera was 36.6% ± 4.9% (range 2.1% to 64.4%) versus -0.6 %±0.1 % (range -1.2% to 0.0%) in normal controls (p<0.0001). Positive controls fMLP and anti-FcRI antibody were 50.5% and 38.5%, respectively. CONCLUSIONS: Sera from patients with chronic urticaria significantly upregulate basophil CD203c. This in vitro assay may provide an easier method to identify patients with autoimmune urticaria and further our understanding of mechanisms of chronic urticaria.
712