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Monoclonal gammopathies of undetermined significance (MGUS) in patients with chronic urticaria (CU)
J ALLERGY CLINIMMUNOL VOLUME 111, NUMBER 2
IL-5R~ regulation in blood and tissue of NP patients. SOL-IL-5Rex correlated well with the severity of disease locally in the nose, but also systemically in the airways. The counter-regulation between the SOL and TM-IL-5Rc~ in polyp tissue points that eosinophils are able to control their responsiveness to IL-5 by regulated expression of the IL-5Rot isoforms.
Funding: Grant Monies
1124
Usefulness of the Basotest to Detect Basoph,l Activating Auto-antibodies in Chronic Idiopathic Urticaria (CIU)
C. Van den K e y b u s I, A. De Swerdt 2, A. Kasran 2, J. L. Ceuppens2; IDepartment of Dermatology, University Hospital, Leuven, BELGIUM, 2Department of Experimental Immunology, Catholic University, Leuven, BELGIUM. RATIONALE: Developing and evaluating a functional assay for detection of auto-antibodies in CIU, comparing it with the autologous serum skin test (ASST) and looking for an association between anti-FceRlat and other auto-antibodies, was the goal. METHODS: Sera of CIU patients were incubated with donor basophils and activation of basophils was determined by CD63 surface expression. RESULTS: When 10,71% of CD63 expressing basophils was taken as lower limit of positivity (= mean CD63 expression in control sera + 2SD), 47% of CIU patients had a positive basotest, while 31% had a positive ASST. Positive basotest was found in 79% of ASST positive patients and in 32% of ASST negative patients (p=0,0039). When both criteria were considered, 53% of the CIU patients had at least one positive test. Other auto-antibodies were detected in 67% of the strongly positive basotests (>20% CD63) and in 27% of the negative or weakly positive basotests (p=0.0098). CONCLUSIONS: The basotest results suggest the presence of basophil activating auto-antibodies in about 50% of CIU patients. Positive ASST patients have a significantly higher prevalence of a positive basotest than negative ASST patients. The combination of both tests might be more useful for detection of auto-antibodies induced CIU. Patients with a strongly positive basotest had a significantly higher prevalence of auto-antibodies.
Funding: Catholic University Leuven
1125
Tota' HistamineContentin B'oodPredictsthe Presenceof Autoantibedies against IgE/IgE-receptor in Patients with Chronic Urticaria
P. S. Skov l, M. H. Platzer l, L. K. Poulsen 2, C. Bindslev-Jensen3; )Allergy Unit-7512, National University Hospital, Copenhagen, DENMARK, 2Allergy Unit-7542, National University Hospital, Copenhagen, DENMARK, 3Allergy Center-Department of Dermatology, Odense University Hospital, Odense, DENMARK. RATIONALE: In patients with Chronic Idiopathic Urticaria (CIU) autoantibodies against IgE/IgE-receptor--demonstrated by serum induced basophil histamine release (HRu-Test)--is often found. An association between total blood level of histamine and autoantibodies was examined. METHODS: White blood cells containing 1-2% basophils from healthy donors were incubated with serum from patients suspected of having CIU (n=822). A subgroup of patients with severe CIU (n=62) were assayed for total blood level of histamine as well and used as an index of circulating basophils. Histamine was measured by the glass fiber method (The Reference Laboratory, Denmark). In HRu-Test a histamine release of > 12.5% is considered positive. RESULTS: A total of 822 patients (254 males) were examined and positive HRu-Test were found in 40.5% females and 41.5% males. A subgroup with severe CIU (n=61), autoantibodies were found in 29 patients (47%). There were significant lower histamine levels in HRu-Test positive (35 _ 21 ng/ml) and negative patients (59 _+21 ng/ml) compared to controls ( 105 -+ 39 ng/ml) (p=0.0038 and p=0.0012 respectively). Blood histamine levels in HRu-test positive patients were significantly lower compared to the HRuTest negative patients (p=0.0082). A histamine level of <47 ng/ml blood predicted 78% of HRu-Test positive patients.
Abstracts $349
CONCLUSIONS: In severe CIU a reduced level of blood histamine was found both in patients with and without autoantibodies. This indicates that factors other than these autoantibodies regulate basophil number and release in patients with CIU.
Funding: The Reference Laboratory"
1 1 2 6 .o.oo,o., ~
o,~176
(MGUS) in Patients with Chronic Urticaria (CU)
M. Karakelides I, K. L. Monson 2, J. J. Jacobsen 2, G. Volcheck 2, J. H. Butterfield 2, C. R. Weiler2; ]Sophie Davis School of Biomedical Education, New York, NY, 2Mayo Clinic, Rochester, MN. RATIONALE: The association of MGUS and CU has been described in Schnitzler's Syndrome. We evaluated this association in our CU population. M E T H O D S : The Mayo Clinic diagnosis database was reviewed for patients with CU only or both CU and MGUS between 1994 and 2001. RESULTS: 1638 patients received a diagnosis of CU during that time period, 2.38% of them had a diagnosis of MGUS. Of those with CU and MGUS 17.94% developed lymphoma and 33.33% had a diagnosis of other malignancies. The monoclonal protein isotypes detected were It, 7, and at. The female to male ratio for the CU group and the MGUS with CU group was 2:1. The mean age of presentation in the group with CU only was 43 in contrast to a mean age of 57 in the group with CU and MGUS (p<0.0001). The negative predictive value for the association of MGUS with CU in patients presenting younger than 43 is 99.04%. CONCLUSION: MGUS in CU patients can be of multiple isotypes and likely represent variants of Schnitzler's Syndrome. The association of MGUS and CU is unlikely in those patients presenting with CU symptoms below the age of 43. If MGUS is diagnosed in a CU patient a diligent search for lymphoma and other malignancies should ensue. IRB B-1739-00.
Funding: Self-funded
1127
Impact of Dealoratadine on Signs, Symptoms,and Quality of Life Measures of Chronic Idiopathic Urticaria (CIU) in Clinical Practice
A. K a p p 1, A. Plenker2; JDepartment of Dermatology, University of Hannover Medical School. Hannover, GERMANY. 2Essex Pharma, Munich, GERMANY. RATIONALE: Controlled trials demonstrate that desloratadine is an effective, well-tolerated treatment for CIU. Post-marketing studies (PMSs) are an important tool to confirm the safety and efficacy of new therapies in the clinical setting. METHODS: We performed a multi-center PMS in Germany in patients > 12 yrs with CIU treated with desloratadine in dermatology practices. At enrolment, a medical history was recorded and itch, number of wheals, diameter of largest wheal, overall CIU severity, impairment of sleep and daily activities were rated using a 4-point scale (0=none-3=severe). Treatment duration was physician-determined. At the end of treatment, C1U symptom severities, assessments of therapeutic response (physician only), and global efficacy and safety (physician and patient) were assessed. Adverse events during the study were recorded and rated for ~verity and relation to desloratadine. RESULTS: The study enrolled 9246 patients (62.5% female, mean age 43.2 yr, mean treatment 40.4 days). Itch, wheal number, size of largest wheal and overall CIU severity scores were reduced significantly with desloratadine (P<0.0001). The impact of CIU on sleep and daily activities fell significantly with desloratadine (P<0.0001), with improvements occurring in 67.3% and 71% of patients, respectively. Complete or significant relief of CIU occurred in 88.3% of patients, while global efficacy was rated excellent/good by 83.6% of physicians and 82.1% of patients. Desloratadine was well tolerated (0.5% adverse event rate, 0% serious); 82% of physicians and 77% of patients assessed safety as excellent. CONCLUSIONS: This study confirms in normal clinical practice the excellent efficacy and safety profile of desloratadine reported in placebocontrolled trials.
Funding: Essex Pharma
IL-5R~ regulation in blood and tissue of NP patients. SOL-IL-5Rex correlated well with the severity of disease locally in the nose, but also systemically in the airways. The counter-regulation between the SOL and TM-IL-5Rc~ in polyp tissue points that eosinophils are able to control their responsiveness to IL-5 by regulated expression of the IL-5Rot isoforms.
Funding: Grant Monies
1124
Usefulness of the Basotest to Detect Basoph,l Activating Auto-antibodies in Chronic Idiopathic Urticaria (CIU)
C. Van den K e y b u s I, A. De Swerdt 2, A. Kasran 2, J. L. Ceuppens2; IDepartment of Dermatology, University Hospital, Leuven, BELGIUM, 2Department of Experimental Immunology, Catholic University, Leuven, BELGIUM. RATIONALE: Developing and evaluating a functional assay for detection of auto-antibodies in CIU, comparing it with the autologous serum skin test (ASST) and looking for an association between anti-FceRlat and other auto-antibodies, was the goal. METHODS: Sera of CIU patients were incubated with donor basophils and activation of basophils was determined by CD63 surface expression. RESULTS: When 10,71% of CD63 expressing basophils was taken as lower limit of positivity (= mean CD63 expression in control sera + 2SD), 47% of CIU patients had a positive basotest, while 31% had a positive ASST. Positive basotest was found in 79% of ASST positive patients and in 32% of ASST negative patients (p=0,0039). When both criteria were considered, 53% of the CIU patients had at least one positive test. Other auto-antibodies were detected in 67% of the strongly positive basotests (>20% CD63) and in 27% of the negative or weakly positive basotests (p=0.0098). CONCLUSIONS: The basotest results suggest the presence of basophil activating auto-antibodies in about 50% of CIU patients. Positive ASST patients have a significantly higher prevalence of a positive basotest than negative ASST patients. The combination of both tests might be more useful for detection of auto-antibodies induced CIU. Patients with a strongly positive basotest had a significantly higher prevalence of auto-antibodies.
Funding: Catholic University Leuven
1125
Tota' HistamineContentin B'oodPredictsthe Presenceof Autoantibedies against IgE/IgE-receptor in Patients with Chronic Urticaria
P. S. Skov l, M. H. Platzer l, L. K. Poulsen 2, C. Bindslev-Jensen3; )Allergy Unit-7512, National University Hospital, Copenhagen, DENMARK, 2Allergy Unit-7542, National University Hospital, Copenhagen, DENMARK, 3Allergy Center-Department of Dermatology, Odense University Hospital, Odense, DENMARK. RATIONALE: In patients with Chronic Idiopathic Urticaria (CIU) autoantibodies against IgE/IgE-receptor--demonstrated by serum induced basophil histamine release (HRu-Test)--is often found. An association between total blood level of histamine and autoantibodies was examined. METHODS: White blood cells containing 1-2% basophils from healthy donors were incubated with serum from patients suspected of having CIU (n=822). A subgroup of patients with severe CIU (n=62) were assayed for total blood level of histamine as well and used as an index of circulating basophils. Histamine was measured by the glass fiber method (The Reference Laboratory, Denmark). In HRu-Test a histamine release of > 12.5% is considered positive. RESULTS: A total of 822 patients (254 males) were examined and positive HRu-Test were found in 40.5% females and 41.5% males. A subgroup with severe CIU (n=61), autoantibodies were found in 29 patients (47%). There were significant lower histamine levels in HRu-Test positive (35 _ 21 ng/ml) and negative patients (59 _+21 ng/ml) compared to controls ( 105 -+ 39 ng/ml) (p=0.0038 and p=0.0012 respectively). Blood histamine levels in HRu-test positive patients were significantly lower compared to the HRuTest negative patients (p=0.0082). A histamine level of <47 ng/ml blood predicted 78% of HRu-Test positive patients.
Abstracts $349
CONCLUSIONS: In severe CIU a reduced level of blood histamine was found both in patients with and without autoantibodies. This indicates that factors other than these autoantibodies regulate basophil number and release in patients with CIU.
Funding: The Reference Laboratory"
1 1 2 6 .o.oo,o., ~
o,~176
(MGUS) in Patients with Chronic Urticaria (CU)
M. Karakelides I, K. L. Monson 2, J. J. Jacobsen 2, G. Volcheck 2, J. H. Butterfield 2, C. R. Weiler2; ]Sophie Davis School of Biomedical Education, New York, NY, 2Mayo Clinic, Rochester, MN. RATIONALE: The association of MGUS and CU has been described in Schnitzler's Syndrome. We evaluated this association in our CU population. M E T H O D S : The Mayo Clinic diagnosis database was reviewed for patients with CU only or both CU and MGUS between 1994 and 2001. RESULTS: 1638 patients received a diagnosis of CU during that time period, 2.38% of them had a diagnosis of MGUS. Of those with CU and MGUS 17.94% developed lymphoma and 33.33% had a diagnosis of other malignancies. The monoclonal protein isotypes detected were It, 7, and at. The female to male ratio for the CU group and the MGUS with CU group was 2:1. The mean age of presentation in the group with CU only was 43 in contrast to a mean age of 57 in the group with CU and MGUS (p<0.0001). The negative predictive value for the association of MGUS with CU in patients presenting younger than 43 is 99.04%. CONCLUSION: MGUS in CU patients can be of multiple isotypes and likely represent variants of Schnitzler's Syndrome. The association of MGUS and CU is unlikely in those patients presenting with CU symptoms below the age of 43. If MGUS is diagnosed in a CU patient a diligent search for lymphoma and other malignancies should ensue. IRB B-1739-00.
Funding: Self-funded
1127
Impact of Dealoratadine on Signs, Symptoms,and Quality of Life Measures of Chronic Idiopathic Urticaria (CIU) in Clinical Practice
A. K a p p 1, A. Plenker2; JDepartment of Dermatology, University of Hannover Medical School. Hannover, GERMANY. 2Essex Pharma, Munich, GERMANY. RATIONALE: Controlled trials demonstrate that desloratadine is an effective, well-tolerated treatment for CIU. Post-marketing studies (PMSs) are an important tool to confirm the safety and efficacy of new therapies in the clinical setting. METHODS: We performed a multi-center PMS in Germany in patients > 12 yrs with CIU treated with desloratadine in dermatology practices. At enrolment, a medical history was recorded and itch, number of wheals, diameter of largest wheal, overall CIU severity, impairment of sleep and daily activities were rated using a 4-point scale (0=none-3=severe). Treatment duration was physician-determined. At the end of treatment, C1U symptom severities, assessments of therapeutic response (physician only), and global efficacy and safety (physician and patient) were assessed. Adverse events during the study were recorded and rated for ~verity and relation to desloratadine. RESULTS: The study enrolled 9246 patients (62.5% female, mean age 43.2 yr, mean treatment 40.4 days). Itch, wheal number, size of largest wheal and overall CIU severity scores were reduced significantly with desloratadine (P<0.0001). The impact of CIU on sleep and daily activities fell significantly with desloratadine (P<0.0001), with improvements occurring in 67.3% and 71% of patients, respectively. Complete or significant relief of CIU occurred in 88.3% of patients, while global efficacy was rated excellent/good by 83.6% of physicians and 82.1% of patients. Desloratadine was well tolerated (0.5% adverse event rate, 0% serious); 82% of physicians and 77% of patients assessed safety as excellent. CONCLUSIONS: This study confirms in normal clinical practice the excellent efficacy and safety profile of desloratadine reported in placebocontrolled trials.
Funding: Essex Pharma