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Clinical Evaluation of Tolerance and Viral Safety of Human C1-inhibitor Concentrate in Patients with Recurrent Angioedema Due to Hereditary (HAE) or Acquired (AAE) C1 Inhibitor Deficiency
472
Study of the Role of Basophils in Skin Biopsies of Urticaria
M. M. Ferrer1, M. A. Idoate2, P. Gil3; 1Allergy and Clinical Immunology, Clinica Universitaria Navarra, Pamplona, SPAIN, 2Pathology, Clinica Universitaria Navarra, Pamplona, SPAIN, 3Dermatology, Clinica Universitaria Navarra, Pamplona, SPAIN. RATIONALE: It has been previously demonstrated that basopenia is more frequent in patients of chronic urticaria, one reason could be that they are recruited on the skin. We wanted to demonstrate the presence of basophils in the skin lesions of tissue of chronic urticaria biopsies. METHODS: We analyzed biopsies of skin lesions of patients suffering from severe chronic urticaria (n=10) by a specific antibody to basophils, 2D7 (clone, 1/150). Other types of urticaria, common urticaria (n=8) and urticaria pigmentosa (n=8), were used as references. We also studied the presence of mast cells in the same samples employing c-kit (DAKO®, 1/100). We utilized also as reference a basophil cell line KU812F and six cases of systemic mastocytosis. RESULTS: We found 2D7+ in biopsies specimens of both common and severe chronic urticaria and in the KU812F cell line. There was no difference in the number of 2D7+ cells in both groups. However, it was surprising that most cells of urticaria pigmentosa expressed 2D7 and the KU812F cell line, but not in systemic mastocitosis. A similar density of mast cells (c-kit +) was observed in both common and chronic urticaria. CONCLUSIONS: We demonstrate that basophil is involved in the development of urticarial lesions. The density of basophils cannot explain the chronicity of urticaria. It is postulated that the basopenia could be justified by the intralessional recruitment of basophils. Funding: Fondo Investigacion Sanitaria grant # 03/0789 Severity of Autoimmune Urticaria is not Different than in Children with Chronic Urticaria from Other Causes P. Sangacharoenkit, S. Pongpreuksa, S. Boonchoo, P. Vichyanond, N. Visitsunthorn, O. Jirapongsananuruk; Allergy and Immunology division, Pediatric department, Siriraj Hospital, Mahidol University, Bangkok, THAILAND. RATIONALE: Autoimmune urticaria (AU) can be found in 40% of adult with chronic urticaria (CU) and is shown to increase severity of this disease necessitating combined therapy or corticosteroid to control the symptoms. OBJECTIVE: To determine the prevalence and severity for AU in children with CU. METHODS: Seventy-two children with CU were evaluated for AU by autologous serum skin test (ASST). Thirty-four (47.2%) children were male. Mean age was 8.75 years. All of them were initially prescribed 2nd generation H1-antihistamine (cetirizine or loratadine). The following treatment regimens were used if symptoms were not controlled: cetirizine or loratadine with hydroxyzine, cetirizine or loratadine with ranitidine and cetirizine or loratadine, ranitidine with montelukast. RESULTS: The prevalence of AU in children with CU was 38.9% (12/34 male, 35.3% and 16/38 female, 42.1%). There was no significant difference in AU between male and female children (Pearson chi-square, p=0.554). Fifteen and 13 children with AU were prescribed monotherapy and combined therapy, respectively, compared with 24 and 20 children with non-AU. There was no significant difference in treatment between AU and non-AU groups (Pearson chi-square, p=0.971). None of the children with CU in our study need corticosteroid. CONCLUSIONS: The prevalence of AU in children is closed to AU in adult. However, AU in children was not as severe as observed in adult AU. Funding: Mahidol University
473
The Utility of Skin Biopsy in the Diagnosis and Management of Chronic Urticaria: Correlation with Response to Antihistamine Therapy M. Punar1, S. Patel2, A. Carlson1, M. Pasha3; 1Pathology and Laboratory Medicine, Albany Medical College, Albany, NY, 2Medicine, Albany Medical College, Albany, NY, 3Allergy and Immunology, Albany Medical College, Albany, NY.
474
RATIONALE: Chronic urticaria (CU), daily hives > 6 weeks, remains a challenging medical problem. The etiology is unknown in most cases and symptomatic treatment with antihistamines is not always effective. METHODS: Thirty consecutive patients referred for evaluation of chronic urticaria who underwent skin punch biopsy, were included in this study. These results were correlated with clinical and laboratory findings. RESULTS: The patients consisted of 27 females and 3 males with an average age of 44, range 8-83years old. Angioedema, hypothyroidism, and atopy (asthma, eczema or allergic rhinitis) were present in 43%, 20% and 30%, respectively. Six patients’ symptoms were controlled with antihistamine therapy (ceterizine, up to 10mg bid); the remainder required additional antihistamines, leukotriene antagonists, and/or other immunomodulators to control their symptoms. By histologic inflammatory reaction pattern, suspected CU patients could be classified into several diagnostic groups: 1) urticarial hypersensitivity reaction (UHR) (19/30, 61%); 2) urticarial vasculitis (3/30, 10%), 3) erythema multiforme-like interface dermatitis (5/30, 17%), 4) delayed type hypersensitivity reaction (2/30, 7%), and 5) palisaded neutrophilic and granulomatous dermatitis (a.k.a. Winkelmann granuloma) (2/30, 7%). A UHR could be further subclassified into either those with a neutrophilic (13/19, 68%) or eosinophilic (6/19, 32%) predominate inflammatory infiltrate. Neutrophilic predominate UHR significantly correlated with failure/poor response to antihistamine therapy (0/13; P=0.005). CONCLUSIONS: We recommend skin biopsy of difficult to control CU patients as it may provide additional information in the management. Chronic urticaria patients with neutrophilic predominate UHR are poor/non- responsive to antihistamine therapy, and thus may require other immunomodulating agents. Clinical Evaluation of Tolerance and Viral Safety of Human C1-inhibitor Concentrate in Patients with Recurrent Angioedema Due to Hereditary (HAE) or Acquired (AAE) C1 Inhibitor Deficiency M. Bulnes; Allergy, Hospital La Paz, Spain, SPAIN. RATIONALE: Background: The therapy of choice of acute attacks of angioedema due to HAE or AAE in Spain is replacement with Human C1INH concentrate (hC1INH). AIMS: To evaluate tolerance and safety of hC1INH before and after introduction of virucidal methods. METHODS: 62 patients with HAE and 4 with AAE followed up in our department since 1978 were included. The observation time ranged from 1 to 26years (mean 6.4 years).Patients were divided into two groups: A: Treated with hC1INH (n=36); B: Never treated with hC1 INH (n=30).Side effects were recorded after use of non pasteurized hC1INH and pasteurized hC1INH. Blood borne viral infections were evaluated by ELISA to HIV, HBV, HCV. RESULTS: A total of 377 infusions (188,500 Units) were administered in 36 patients (median=4.0,range: 1-120 infusions). hC1INH was used for acute treatment in 24 patients, short term prophylaxis in 20 and long term prophylaxis in 1 patient . No significant side effects during infusion were recorded. One patient developed non A non B hepatitis in 1983, two months after administration of non-pasteurized plasma C1 inhibitor. Later a positive test for HCV was found. A positive test for HBV was detected in one patient several years after use of non-virus-inactivated concentrate, not clearly attributable to its use. No patient had any seroconversion to HCV, HBV or HIV attributable to use of pasteurized hC1INH (Berinert™, ZLB-Behring, Malburg, Germany). CONCLUSIONS: Pasteurized hC1INH (Berinert™) in use in Spain since 1990´s is well tolerated and has significantly decreased the risk of blood.
475
SUNDAY
Abstracts S121
J ALLERGY CLIN IMMUNOL VOLUME 117, NUMBER 2
Study of the Role of Basophils in Skin Biopsies of Urticaria
M. M. Ferrer1, M. A. Idoate2, P. Gil3; 1Allergy and Clinical Immunology, Clinica Universitaria Navarra, Pamplona, SPAIN, 2Pathology, Clinica Universitaria Navarra, Pamplona, SPAIN, 3Dermatology, Clinica Universitaria Navarra, Pamplona, SPAIN. RATIONALE: It has been previously demonstrated that basopenia is more frequent in patients of chronic urticaria, one reason could be that they are recruited on the skin. We wanted to demonstrate the presence of basophils in the skin lesions of tissue of chronic urticaria biopsies. METHODS: We analyzed biopsies of skin lesions of patients suffering from severe chronic urticaria (n=10) by a specific antibody to basophils, 2D7 (clone, 1/150). Other types of urticaria, common urticaria (n=8) and urticaria pigmentosa (n=8), were used as references. We also studied the presence of mast cells in the same samples employing c-kit (DAKO®, 1/100). We utilized also as reference a basophil cell line KU812F and six cases of systemic mastocytosis. RESULTS: We found 2D7+ in biopsies specimens of both common and severe chronic urticaria and in the KU812F cell line. There was no difference in the number of 2D7+ cells in both groups. However, it was surprising that most cells of urticaria pigmentosa expressed 2D7 and the KU812F cell line, but not in systemic mastocitosis. A similar density of mast cells (c-kit +) was observed in both common and chronic urticaria. CONCLUSIONS: We demonstrate that basophil is involved in the development of urticarial lesions. The density of basophils cannot explain the chronicity of urticaria. It is postulated that the basopenia could be justified by the intralessional recruitment of basophils. Funding: Fondo Investigacion Sanitaria grant # 03/0789 Severity of Autoimmune Urticaria is not Different than in Children with Chronic Urticaria from Other Causes P. Sangacharoenkit, S. Pongpreuksa, S. Boonchoo, P. Vichyanond, N. Visitsunthorn, O. Jirapongsananuruk; Allergy and Immunology division, Pediatric department, Siriraj Hospital, Mahidol University, Bangkok, THAILAND. RATIONALE: Autoimmune urticaria (AU) can be found in 40% of adult with chronic urticaria (CU) and is shown to increase severity of this disease necessitating combined therapy or corticosteroid to control the symptoms. OBJECTIVE: To determine the prevalence and severity for AU in children with CU. METHODS: Seventy-two children with CU were evaluated for AU by autologous serum skin test (ASST). Thirty-four (47.2%) children were male. Mean age was 8.75 years. All of them were initially prescribed 2nd generation H1-antihistamine (cetirizine or loratadine). The following treatment regimens were used if symptoms were not controlled: cetirizine or loratadine with hydroxyzine, cetirizine or loratadine with ranitidine and cetirizine or loratadine, ranitidine with montelukast. RESULTS: The prevalence of AU in children with CU was 38.9% (12/34 male, 35.3% and 16/38 female, 42.1%). There was no significant difference in AU between male and female children (Pearson chi-square, p=0.554). Fifteen and 13 children with AU were prescribed monotherapy and combined therapy, respectively, compared with 24 and 20 children with non-AU. There was no significant difference in treatment between AU and non-AU groups (Pearson chi-square, p=0.971). None of the children with CU in our study need corticosteroid. CONCLUSIONS: The prevalence of AU in children is closed to AU in adult. However, AU in children was not as severe as observed in adult AU. Funding: Mahidol University
473
The Utility of Skin Biopsy in the Diagnosis and Management of Chronic Urticaria: Correlation with Response to Antihistamine Therapy M. Punar1, S. Patel2, A. Carlson1, M. Pasha3; 1Pathology and Laboratory Medicine, Albany Medical College, Albany, NY, 2Medicine, Albany Medical College, Albany, NY, 3Allergy and Immunology, Albany Medical College, Albany, NY.
474
RATIONALE: Chronic urticaria (CU), daily hives > 6 weeks, remains a challenging medical problem. The etiology is unknown in most cases and symptomatic treatment with antihistamines is not always effective. METHODS: Thirty consecutive patients referred for evaluation of chronic urticaria who underwent skin punch biopsy, were included in this study. These results were correlated with clinical and laboratory findings. RESULTS: The patients consisted of 27 females and 3 males with an average age of 44, range 8-83years old. Angioedema, hypothyroidism, and atopy (asthma, eczema or allergic rhinitis) were present in 43%, 20% and 30%, respectively. Six patients’ symptoms were controlled with antihistamine therapy (ceterizine, up to 10mg bid); the remainder required additional antihistamines, leukotriene antagonists, and/or other immunomodulators to control their symptoms. By histologic inflammatory reaction pattern, suspected CU patients could be classified into several diagnostic groups: 1) urticarial hypersensitivity reaction (UHR) (19/30, 61%); 2) urticarial vasculitis (3/30, 10%), 3) erythema multiforme-like interface dermatitis (5/30, 17%), 4) delayed type hypersensitivity reaction (2/30, 7%), and 5) palisaded neutrophilic and granulomatous dermatitis (a.k.a. Winkelmann granuloma) (2/30, 7%). A UHR could be further subclassified into either those with a neutrophilic (13/19, 68%) or eosinophilic (6/19, 32%) predominate inflammatory infiltrate. Neutrophilic predominate UHR significantly correlated with failure/poor response to antihistamine therapy (0/13; P=0.005). CONCLUSIONS: We recommend skin biopsy of difficult to control CU patients as it may provide additional information in the management. Chronic urticaria patients with neutrophilic predominate UHR are poor/non- responsive to antihistamine therapy, and thus may require other immunomodulating agents. Clinical Evaluation of Tolerance and Viral Safety of Human C1-inhibitor Concentrate in Patients with Recurrent Angioedema Due to Hereditary (HAE) or Acquired (AAE) C1 Inhibitor Deficiency M. Bulnes; Allergy, Hospital La Paz, Spain, SPAIN. RATIONALE: Background: The therapy of choice of acute attacks of angioedema due to HAE or AAE in Spain is replacement with Human C1INH concentrate (hC1INH). AIMS: To evaluate tolerance and safety of hC1INH before and after introduction of virucidal methods. METHODS: 62 patients with HAE and 4 with AAE followed up in our department since 1978 were included. The observation time ranged from 1 to 26years (mean 6.4 years).Patients were divided into two groups: A: Treated with hC1INH (n=36); B: Never treated with hC1 INH (n=30).Side effects were recorded after use of non pasteurized hC1INH and pasteurized hC1INH. Blood borne viral infections were evaluated by ELISA to HIV, HBV, HCV. RESULTS: A total of 377 infusions (188,500 Units) were administered in 36 patients (median=4.0,range: 1-120 infusions). hC1INH was used for acute treatment in 24 patients, short term prophylaxis in 20 and long term prophylaxis in 1 patient . No significant side effects during infusion were recorded. One patient developed non A non B hepatitis in 1983, two months after administration of non-pasteurized plasma C1 inhibitor. Later a positive test for HCV was found. A positive test for HBV was detected in one patient several years after use of non-virus-inactivated concentrate, not clearly attributable to its use. No patient had any seroconversion to HCV, HBV or HIV attributable to use of pasteurized hC1INH (Berinert™, ZLB-Behring, Malburg, Germany). CONCLUSIONS: Pasteurized hC1INH (Berinert™) in use in Spain since 1990´s is well tolerated and has significantly decreased the risk of blood.
475
SUNDAY
Abstracts S121
J ALLERGY CLIN IMMUNOL VOLUME 117, NUMBER 2