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Clinical Characteristics of Acetyl Salicylic Acid (ASA) Intolerant Urticaria: Is There Any Differences between Acute and Chronic ASA Intolerant Urticaria?
AB96 Abstracts
377
SUNDAY
Use of Tacrolimus in the Management of Refractory Chronic Urticaria S. Boos, D. Khan; UTSW, Dallas, TX. RATIONALE: Chronic urticaria (CU) causes significant morbidity. Many patients do not achieve adequate control with conventional antihistamine therapy; others require long term corticosteroids, with significant adverse effects. Numerous alternatives have been used including calcineurin inhibitors, primarily cyclosporine. We sought to determine the safety and effectiveness of the calcineurin inhibitor tacrolimus. METHODS: A retrospective chart review was conducted of adult CU patients who were treated with tacrolimus in our allergy clinic. Laboratory values and clinical evidence for toxicity were abstracted as well as physician reports of efficacy. RESULTS: Sixteen adults with CU treated with tacrolimus were identified. All patients were refractory to both 1st and 2nd generation antihistamines, and 50% were on daily prednisone (mean dose of 20mg/day). Ninety-four percent had failed alternative medications, including montelukast, sulfasalazine, dapsone, hydroxychloroquine, colchicine and thyroxine. Mean duration of symptoms prior to starting tacrolimus was approximately 6 years. Tacrolimus dosing ranged from 1mg-8mg/day. Fourteen patients (88%) improved with tacrolimus, most within 1 month. Fifty percent were able to discontinue daily prednisone, and 25% were able to decrease Prednisone dose by >50%. Ten of sixteen reported adverse effects, most commonly gastrointestinal symptoms or dysesthesias. Three had elevated creatinine levels. Two discontinued tacrolimus because of adverse effects. Three patients required a second course of tacrolimus due to recurrent CU, and two achieved remission with this second course. CONCLUSIONS: Tacrolimus appears to be an effective alternative agent for management of refractory chronic urticaria patients. While adverse effects were common, most were benign and dose related.
378
A Retrospective Chart Review Of The Use Of Colchicine For The Treatment Of Refractory Chronic Idiopathic Urticaria M. S. Georgy, L. C. Grammer, P. A. Greenberger, A. T. Peters; Northwestern University Feinberg School of Medicine, Chicago, IL. RATIONALE: Colchicine, a microtubule polymerization inhibitor, may be effective in the treatment of chronic idiopathic urticaria (CIU) because it suppresses mast cell degranulation and leukotriene generation. METHODS: Charts of 55 patients with CIU treated with greater than 7 days of colchicine were reviewed for the following: type of urticaria, type of response, and oral steroid therapy before and after colchicine initiation. The number of steroid courses or the number of exacerbations requiring an increase in baseline steroid dose was tabulated for a minimum of 6 months before and after starting colchicine. Response was defined as subjective improvement and a decrease of at least 50% in oral steroid dose within 3 months of starting colchicine. A partial response was defined as subjective improvement without a decrease in oral steroids by 50% within 3 months of starting colchicine. RESULTS: 24 (44%) patients were responders, 29 (53%) were non-responders, and 2 (4%) were partial-responders. The number of steroid courses before and after colchicine initiation was significantly decreased in the responders (2.44 vs 0.33, P<0.05). Skin biopsies were performed in 27 patients (14 responders, 12 non-responders, 1 partial responder). Skin biopsies showed neutrophilic urticaria in 86% of responders and 25% of non-responders. CONCLUSION: Colchicine is an effective steroid-sparing agent which may be used for the treatment of refractory CIU.
J ALLERGY CLIN IMMUNOL FEBRUARY 2010
379
Lack of Cross-Reactive Thyroid Antibodies in Chronic Idiopathic Urticaria (CIU) L. Borish1, A. Tinana2, J. Steinke1, J. Mozena1; 1University of Virginia, Charlottesville, VA, 2University of Texas Medical Branch, Galveston, TX. RATIONALE: CIU auto-antibodies are directed against FceR1a on mast cells. In addition, approximately 30% of CIU patients have autoimmune thyroiditis. No current data exist to suggest that anti-thyroid antibodies play a direct role in the degranulation of mast cells in CIU as opposed to merely reflecting a shared genetic predisposition for the development of autoimmune illnesses. We investigated whether the high incidence of Hashimoto’s thyroiditis (HT) found in patients with CIU could be explained by epitope cross-reactivity of FceRIa with thyroid antigens. METHODS: CIU patients with both anti-thyroid and anti-FceRIa antibodies were enrolled. Inhibition assays were performed by incubating CIU sera overnight with recombinant human FceRIa, recombinant human thyroglobulin (TG) or recombinant human thyroid peroxidase (TPO). All samples were then assayed for the presence of anti-FceRIa antibodies by ELISA. Utilizing an immortalized human mast cell line (LUVA), production of cysteinyl leukotrienes was measured after incubating sera with excess TPO or TG overnight. RESULTS: In CIU patients who possess anti-FceR1a antibodies and thyroid autoantibodies, the detection of anti-FceR1a antibodies was inhibited by excess FceRIa (p<0.01) but not excess TPO or TG. Similarly, we found no inhibition of cysteinyl leukotriene production after incubating with thyroid antigens overnight. CONCLUSIONS: Recombinant FceRIa significantly inhibits the detection of anti-FceRIa antibodies in patients with CIU/HT whereas thyroid antigens do not. Epitopic cross-reactivity of anti-FceRIa antibodies does not explain the high prevalence of anti-thyroid antibodies found in patients with CIU. Therefore, the high incidence of HTassociated with CIU appears to be due to a genetic predisposition for autoimmune diseases.
380
Clinical Characteristics of Acetyl Salicylic Acid (ASA) Intolerant Urticaria: Is There Any Differences between Acute and Chronic ASA Intolerant Urticaria? J. Kim, J. Kim, G. Choi, Y. Ye, D. Nahm, H. Park; Ajou University School of Medicine, Suwon, REPUBLIC OF KOREA. RATIONALE: We observed the clinical features of ASA intolerant urticaria (AIU) patients, including atopic status, associated allergic diseases and immunologic findings, and investigated any differences between acute (AIAU) and chronic (AICU) ASA intolerant urticaria. METHODS: 232 AIAU patients, 244 AICU patients and 232 non-atopic normal controls (NC) were enrolled. ASA sensitivity was confirmed by the result of oral aspirin provocation test. AICU was defined as those with chronic urticaria showing urticaria exacerbation by ASA, while AIAU was defined as those developing urticaria when exposed to ASA, and otherwise normal. Atopy was determined by positive skin prick test result to at least one common inhalant allergen. Serum total IgE, specific IgE to house dust mites and three Staphylococcal superantigens (SEA, SEB, TSST-1) were measured by immunoCAP system (Phadia). Antoantibodies including ANA, anti-thyroglobulin and anti-microsomal, and anti-cytokeratin 14 antibodies were measured by ELISA. HLADRB1*1302 and DQB1*0609 were analyzed by high resolution technique. RESULTS: The atopy rate, serum total and specific IgE to house dust mites and TSST-1 were significantly higher in both AIAU and AICU groups compared to NC, while no significant differences were noted between two groups. Moreover, no significant differences were noted in prevalence of associated allergic diseases, serum autoantibodies and the HLA haplotype, DRB1*1302-DQB1*0609 between two groups. CONCLUSIONS: Atopy is a common predisposing factor for both AIAU and AICU phenotype. No differences were found in clinical parameters between AIAU and AICU. Further investigations will be needed to find a new biomarker for differentiating two phenotypes of AIU.
377
SUNDAY
Use of Tacrolimus in the Management of Refractory Chronic Urticaria S. Boos, D. Khan; UTSW, Dallas, TX. RATIONALE: Chronic urticaria (CU) causes significant morbidity. Many patients do not achieve adequate control with conventional antihistamine therapy; others require long term corticosteroids, with significant adverse effects. Numerous alternatives have been used including calcineurin inhibitors, primarily cyclosporine. We sought to determine the safety and effectiveness of the calcineurin inhibitor tacrolimus. METHODS: A retrospective chart review was conducted of adult CU patients who were treated with tacrolimus in our allergy clinic. Laboratory values and clinical evidence for toxicity were abstracted as well as physician reports of efficacy. RESULTS: Sixteen adults with CU treated with tacrolimus were identified. All patients were refractory to both 1st and 2nd generation antihistamines, and 50% were on daily prednisone (mean dose of 20mg/day). Ninety-four percent had failed alternative medications, including montelukast, sulfasalazine, dapsone, hydroxychloroquine, colchicine and thyroxine. Mean duration of symptoms prior to starting tacrolimus was approximately 6 years. Tacrolimus dosing ranged from 1mg-8mg/day. Fourteen patients (88%) improved with tacrolimus, most within 1 month. Fifty percent were able to discontinue daily prednisone, and 25% were able to decrease Prednisone dose by >50%. Ten of sixteen reported adverse effects, most commonly gastrointestinal symptoms or dysesthesias. Three had elevated creatinine levels. Two discontinued tacrolimus because of adverse effects. Three patients required a second course of tacrolimus due to recurrent CU, and two achieved remission with this second course. CONCLUSIONS: Tacrolimus appears to be an effective alternative agent for management of refractory chronic urticaria patients. While adverse effects were common, most were benign and dose related.
378
A Retrospective Chart Review Of The Use Of Colchicine For The Treatment Of Refractory Chronic Idiopathic Urticaria M. S. Georgy, L. C. Grammer, P. A. Greenberger, A. T. Peters; Northwestern University Feinberg School of Medicine, Chicago, IL. RATIONALE: Colchicine, a microtubule polymerization inhibitor, may be effective in the treatment of chronic idiopathic urticaria (CIU) because it suppresses mast cell degranulation and leukotriene generation. METHODS: Charts of 55 patients with CIU treated with greater than 7 days of colchicine were reviewed for the following: type of urticaria, type of response, and oral steroid therapy before and after colchicine initiation. The number of steroid courses or the number of exacerbations requiring an increase in baseline steroid dose was tabulated for a minimum of 6 months before and after starting colchicine. Response was defined as subjective improvement and a decrease of at least 50% in oral steroid dose within 3 months of starting colchicine. A partial response was defined as subjective improvement without a decrease in oral steroids by 50% within 3 months of starting colchicine. RESULTS: 24 (44%) patients were responders, 29 (53%) were non-responders, and 2 (4%) were partial-responders. The number of steroid courses before and after colchicine initiation was significantly decreased in the responders (2.44 vs 0.33, P<0.05). Skin biopsies were performed in 27 patients (14 responders, 12 non-responders, 1 partial responder). Skin biopsies showed neutrophilic urticaria in 86% of responders and 25% of non-responders. CONCLUSION: Colchicine is an effective steroid-sparing agent which may be used for the treatment of refractory CIU.
J ALLERGY CLIN IMMUNOL FEBRUARY 2010
379
Lack of Cross-Reactive Thyroid Antibodies in Chronic Idiopathic Urticaria (CIU) L. Borish1, A. Tinana2, J. Steinke1, J. Mozena1; 1University of Virginia, Charlottesville, VA, 2University of Texas Medical Branch, Galveston, TX. RATIONALE: CIU auto-antibodies are directed against FceR1a on mast cells. In addition, approximately 30% of CIU patients have autoimmune thyroiditis. No current data exist to suggest that anti-thyroid antibodies play a direct role in the degranulation of mast cells in CIU as opposed to merely reflecting a shared genetic predisposition for the development of autoimmune illnesses. We investigated whether the high incidence of Hashimoto’s thyroiditis (HT) found in patients with CIU could be explained by epitope cross-reactivity of FceRIa with thyroid antigens. METHODS: CIU patients with both anti-thyroid and anti-FceRIa antibodies were enrolled. Inhibition assays were performed by incubating CIU sera overnight with recombinant human FceRIa, recombinant human thyroglobulin (TG) or recombinant human thyroid peroxidase (TPO). All samples were then assayed for the presence of anti-FceRIa antibodies by ELISA. Utilizing an immortalized human mast cell line (LUVA), production of cysteinyl leukotrienes was measured after incubating sera with excess TPO or TG overnight. RESULTS: In CIU patients who possess anti-FceR1a antibodies and thyroid autoantibodies, the detection of anti-FceR1a antibodies was inhibited by excess FceRIa (p<0.01) but not excess TPO or TG. Similarly, we found no inhibition of cysteinyl leukotriene production after incubating with thyroid antigens overnight. CONCLUSIONS: Recombinant FceRIa significantly inhibits the detection of anti-FceRIa antibodies in patients with CIU/HT whereas thyroid antigens do not. Epitopic cross-reactivity of anti-FceRIa antibodies does not explain the high prevalence of anti-thyroid antibodies found in patients with CIU. Therefore, the high incidence of HTassociated with CIU appears to be due to a genetic predisposition for autoimmune diseases.
380
Clinical Characteristics of Acetyl Salicylic Acid (ASA) Intolerant Urticaria: Is There Any Differences between Acute and Chronic ASA Intolerant Urticaria? J. Kim, J. Kim, G. Choi, Y. Ye, D. Nahm, H. Park; Ajou University School of Medicine, Suwon, REPUBLIC OF KOREA. RATIONALE: We observed the clinical features of ASA intolerant urticaria (AIU) patients, including atopic status, associated allergic diseases and immunologic findings, and investigated any differences between acute (AIAU) and chronic (AICU) ASA intolerant urticaria. METHODS: 232 AIAU patients, 244 AICU patients and 232 non-atopic normal controls (NC) were enrolled. ASA sensitivity was confirmed by the result of oral aspirin provocation test. AICU was defined as those with chronic urticaria showing urticaria exacerbation by ASA, while AIAU was defined as those developing urticaria when exposed to ASA, and otherwise normal. Atopy was determined by positive skin prick test result to at least one common inhalant allergen. Serum total IgE, specific IgE to house dust mites and three Staphylococcal superantigens (SEA, SEB, TSST-1) were measured by immunoCAP system (Phadia). Antoantibodies including ANA, anti-thyroglobulin and anti-microsomal, and anti-cytokeratin 14 antibodies were measured by ELISA. HLADRB1*1302 and DQB1*0609 were analyzed by high resolution technique. RESULTS: The atopy rate, serum total and specific IgE to house dust mites and TSST-1 were significantly higher in both AIAU and AICU groups compared to NC, while no significant differences were noted between two groups. Moreover, no significant differences were noted in prevalence of associated allergic diseases, serum autoantibodies and the HLA haplotype, DRB1*1302-DQB1*0609 between two groups. CONCLUSIONS: Atopy is a common predisposing factor for both AIAU and AICU phenotype. No differences were found in clinical parameters between AIAU and AICU. Further investigations will be needed to find a new biomarker for differentiating two phenotypes of AIU.