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P100 Effect of IVIG on acquired angioedema in a patient with specific antibody deficiency
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 117 (2016) S22eS124
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described in the literature to date. When common etiologies have been ruled out during the evaluation of acute angioedema, iron studies should be considered in these patients, especially young menstruating females.
Conclusion: For patients with idiopathic angioedema who do not respond to high dose antihistamine, dapsone seems to be an effective and safe option.
P100
HAE WITH NORMAL C1 INHIBITOR (C1INH) AND FACTOR XII MUTATION A. Doshi*1, M. Riedl2, 1. Whittier, CA; 2. La Jolla, CA.
EFFECT OF IVIG ON ACQUIRED ANGIOEDEMA IN A PATIENT WITH SPECIFIC ANTIBODY DEFICIENCY R. Eisenberg*1, J. Toh2, A. Rubinstein1, 1. Bronx, NY; 2. New York, NY. Introduction: Acquired Angioedema is characterized by episodes of angioedema involving the face, upper airway and small bowel. Treatment includes C1 esterase inhibitor (C1-INH), kallikrein inhibitor and bradykinin antagonists. Prophylaxis with antifibrinolytics, attenuated androgens and regular infusion of C1 inhibitor replacement are used in patients with frequent episodes. We describe a case of acquired angioedema, where monthly IVIG for the treatment of specific antibody deficiency concurrently decreased the frequency of angioedema episodes. Methods: Case Description Results: PV is a 70 year old woman with a history of recurrent infections and thrombocytopenia. She presented with several episodes of angioedema affecting the face, oropharynx, extremities and small bowel. Despite treatment with C1-INH, aminocaproic acid and icatibant, she continued to have events increasing to 3-4 times per week. Triggers were upper respiratory infections and surgery. Workup showed C4 complement 2 (17-64mg/dL), C1q <3.6 (5.0-8.6 mg/dL), C1-INH <3 (21-39mg/dL), C1-INH functional level 13% (>68%) and detectable C1INH autoantibody 0.9, consistent with a diagnosis of acquired angioedema. Immunodeficiency workup revealed slightly decreased immunoglobulin levels and persistently low titers to streptococcus pneumoniae status post vaccination twice (3/14 titers protected, >1.3mcg). IVIG was initiated, along with C1-INH, icatibant, and aminocaproic acid was discontinued. It was only after initiation of IVIG therapy that her angioedema events decreased to three times per month. Conclusions: We describe a case where IVIG, used for treatment of specific antibody deficiency, was found to significantly improve events of angioedema.
P101 DAPSONE IN THE TREATMENT OF IDIOPATHIC ANGIOEDEMA N. Zhu*, W. Stafford, Corpus Christi, TX. Background: For patients with idiopathic angioedema unresponsive to high dose antihistamine, there is no established treatment. Rationale: Dapsone has been shown to be effective in the treatment of idiopathic urticaria, but its efficacy in the treatment of isolated idiopathic angioedema remains unknown. Case Presentation: Case 1 is an 8 year old Hispanic male with a history of recurrent severe eyelid swelling starting at age two. Case 2 is a 42 year old Caucasian male with a history of recurrent angioedema affected his hands, feet, shoulder, eyelids, lips and genitalia for 20 years. Both cases were ruled out allergic and hereditary angioedema based on histories and laboratory studies including C4, C1 inhibitor, tryptase, Factor XII gene Mutation assay, food antibody testing. In both cases, treatments with steroid, antihistamine, and epinephrine in acute episodes were not beneficial. High dose antihistamines (cetirizine 10 mg BID in case 1, cetirizine 10 mg BID, fexofenadine 180 mg BID plus Singulair daily in case 2) were not helpful in preventing recurrences of the swelling. Following initiation of treatment with dapsone 25 mg BID in case 1, the patient has had only one mild episode of angioedema in 10 months. No treatment side effects were noted. In case 2, Treatment with dapsone 100 mg once daily has prevented any recurrences in the last 14 months. Dapsone induced a mild reduction in his hemoglobin.
P102
Introduction: HAE with normal C1 inhibitor (C1INH), despite being described in the literature, is a difficult diagnosis due to a lack of diagnostic tests. Factor XII mutation analysis is potentially useful in confirming the diagnosis. Methods: Description of clinical presentation and laboratory confirmation of Factor XII mutation. Results: A 41-year-old woman presented for evaluation of recurrent facial cutaneous swelling which began at age 28. Over the next several years, she experienced swelling approximately once per year. She sought care, but no diagnosis was made. Following the birth of her first child at age 40, her symptoms worsened, with more frequent and severe swelling involving her face, fingers, toes, airway and genitalia. Her family history was notable for recurring swelling in multiple female family members. Laboratory testing revealed normal C1 inhibitor function of 90%, C1 of 24, and C4 of 12. A factor XII mutation analysis demonstrated heterozygosity for one codon mutation, in which the amino acid lysine was substituted for threonine. Conclusion: The diagnosis and treatment of HAE with normal C1INH is often delayed due to lack of confirmatory diagnostic testing. HAE with normal C1INH was initially described 15 years ago. More recently and primarily in European populations, cases have been associated with a putative gain of function mutation in factor XII. Patients with factor XII mutation are only a minor subset of patients with HAE with normal C1INH, thus there is a need for more research to elucidate the mechanism of disease and improved diagnostics to aid in securing this diagnosis.
P103 ACQUIRED ANGIOEDEMA: A RARE PRESENTATION OF SPLENIC MARGINAL ZONE B-CELL LYMPHOMA T. Basen*1, M. Gianos2, J. Yusin3, 1. Los Angeles, CA; 2. Camarillo, CA; 3. Stevenson Ranch, CA. Introduction: Acquired angioedema in older patients is often the initial presentation of an underlying disorder. Many patients will eventually present with a malignant disorder, often a B-cell lymphoproliferative disorder. It is thus important to confirm the diagnosis so that treatment can begin immediately. Our patient presents with new onset facial swelling from acquired angioedema who is subsequently diagnosed with splenic marginal zone-B-celllymphoma. Methods: The patient was treated with rituximab to complete a total of two years and prescribed ecallantide in the event of another episode of angioedema. Results: This 62-year-old female with a history of hypothyroidism presented with three separate episodes of swelling of her lips and face requiring steroids and antihistamines. She denied unintentional weight loss or fevers but did note persistent fatigue. Her family history is notable for acute leukemia in her father and Sjogren’s disease and lupus in her mother. Her workup for aeroallergen and food allergy, autoimmune diseases, and immunodeficiency were all negative. However, she had decreased levels of C1 esterase inhibitor of 3mg/dl, C1 inhibitor function of 2% (<40% abnormal) and C1q of 3.6mg/dl confirming acquired angioedema. Ultimately, bone marrow biopsy and cytogenetic analysis confirmed splenic marginal zone B-cell lymphoma. The patient was started on rituximab, her fatigue improved, and her c1 esterase inhibitor quantitative and qualitative levels normalized. Since
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described in the literature to date. When common etiologies have been ruled out during the evaluation of acute angioedema, iron studies should be considered in these patients, especially young menstruating females.
Conclusion: For patients with idiopathic angioedema who do not respond to high dose antihistamine, dapsone seems to be an effective and safe option.
P100
HAE WITH NORMAL C1 INHIBITOR (C1INH) AND FACTOR XII MUTATION A. Doshi*1, M. Riedl2, 1. Whittier, CA; 2. La Jolla, CA.
EFFECT OF IVIG ON ACQUIRED ANGIOEDEMA IN A PATIENT WITH SPECIFIC ANTIBODY DEFICIENCY R. Eisenberg*1, J. Toh2, A. Rubinstein1, 1. Bronx, NY; 2. New York, NY. Introduction: Acquired Angioedema is characterized by episodes of angioedema involving the face, upper airway and small bowel. Treatment includes C1 esterase inhibitor (C1-INH), kallikrein inhibitor and bradykinin antagonists. Prophylaxis with antifibrinolytics, attenuated androgens and regular infusion of C1 inhibitor replacement are used in patients with frequent episodes. We describe a case of acquired angioedema, where monthly IVIG for the treatment of specific antibody deficiency concurrently decreased the frequency of angioedema episodes. Methods: Case Description Results: PV is a 70 year old woman with a history of recurrent infections and thrombocytopenia. She presented with several episodes of angioedema affecting the face, oropharynx, extremities and small bowel. Despite treatment with C1-INH, aminocaproic acid and icatibant, she continued to have events increasing to 3-4 times per week. Triggers were upper respiratory infections and surgery. Workup showed C4 complement 2 (17-64mg/dL), C1q <3.6 (5.0-8.6 mg/dL), C1-INH <3 (21-39mg/dL), C1-INH functional level 13% (>68%) and detectable C1INH autoantibody 0.9, consistent with a diagnosis of acquired angioedema. Immunodeficiency workup revealed slightly decreased immunoglobulin levels and persistently low titers to streptococcus pneumoniae status post vaccination twice (3/14 titers protected, >1.3mcg). IVIG was initiated, along with C1-INH, icatibant, and aminocaproic acid was discontinued. It was only after initiation of IVIG therapy that her angioedema events decreased to three times per month. Conclusions: We describe a case where IVIG, used for treatment of specific antibody deficiency, was found to significantly improve events of angioedema.
P101 DAPSONE IN THE TREATMENT OF IDIOPATHIC ANGIOEDEMA N. Zhu*, W. Stafford, Corpus Christi, TX. Background: For patients with idiopathic angioedema unresponsive to high dose antihistamine, there is no established treatment. Rationale: Dapsone has been shown to be effective in the treatment of idiopathic urticaria, but its efficacy in the treatment of isolated idiopathic angioedema remains unknown. Case Presentation: Case 1 is an 8 year old Hispanic male with a history of recurrent severe eyelid swelling starting at age two. Case 2 is a 42 year old Caucasian male with a history of recurrent angioedema affected his hands, feet, shoulder, eyelids, lips and genitalia for 20 years. Both cases were ruled out allergic and hereditary angioedema based on histories and laboratory studies including C4, C1 inhibitor, tryptase, Factor XII gene Mutation assay, food antibody testing. In both cases, treatments with steroid, antihistamine, and epinephrine in acute episodes were not beneficial. High dose antihistamines (cetirizine 10 mg BID in case 1, cetirizine 10 mg BID, fexofenadine 180 mg BID plus Singulair daily in case 2) were not helpful in preventing recurrences of the swelling. Following initiation of treatment with dapsone 25 mg BID in case 1, the patient has had only one mild episode of angioedema in 10 months. No treatment side effects were noted. In case 2, Treatment with dapsone 100 mg once daily has prevented any recurrences in the last 14 months. Dapsone induced a mild reduction in his hemoglobin.
P102
Introduction: HAE with normal C1 inhibitor (C1INH), despite being described in the literature, is a difficult diagnosis due to a lack of diagnostic tests. Factor XII mutation analysis is potentially useful in confirming the diagnosis. Methods: Description of clinical presentation and laboratory confirmation of Factor XII mutation. Results: A 41-year-old woman presented for evaluation of recurrent facial cutaneous swelling which began at age 28. Over the next several years, she experienced swelling approximately once per year. She sought care, but no diagnosis was made. Following the birth of her first child at age 40, her symptoms worsened, with more frequent and severe swelling involving her face, fingers, toes, airway and genitalia. Her family history was notable for recurring swelling in multiple female family members. Laboratory testing revealed normal C1 inhibitor function of 90%, C1 of 24, and C4 of 12. A factor XII mutation analysis demonstrated heterozygosity for one codon mutation, in which the amino acid lysine was substituted for threonine. Conclusion: The diagnosis and treatment of HAE with normal C1INH is often delayed due to lack of confirmatory diagnostic testing. HAE with normal C1INH was initially described 15 years ago. More recently and primarily in European populations, cases have been associated with a putative gain of function mutation in factor XII. Patients with factor XII mutation are only a minor subset of patients with HAE with normal C1INH, thus there is a need for more research to elucidate the mechanism of disease and improved diagnostics to aid in securing this diagnosis.
P103 ACQUIRED ANGIOEDEMA: A RARE PRESENTATION OF SPLENIC MARGINAL ZONE B-CELL LYMPHOMA T. Basen*1, M. Gianos2, J. Yusin3, 1. Los Angeles, CA; 2. Camarillo, CA; 3. Stevenson Ranch, CA. Introduction: Acquired angioedema in older patients is often the initial presentation of an underlying disorder. Many patients will eventually present with a malignant disorder, often a B-cell lymphoproliferative disorder. It is thus important to confirm the diagnosis so that treatment can begin immediately. Our patient presents with new onset facial swelling from acquired angioedema who is subsequently diagnosed with splenic marginal zone-B-celllymphoma. Methods: The patient was treated with rituximab to complete a total of two years and prescribed ecallantide in the event of another episode of angioedema. Results: This 62-year-old female with a history of hypothyroidism presented with three separate episodes of swelling of her lips and face requiring steroids and antihistamines. She denied unintentional weight loss or fevers but did note persistent fatigue. Her family history is notable for acute leukemia in her father and Sjogren’s disease and lupus in her mother. Her workup for aeroallergen and food allergy, autoimmune diseases, and immunodeficiency were all negative. However, she had decreased levels of C1 esterase inhibitor of 3mg/dl, C1 inhibitor function of 2% (<40% abnormal) and C1q of 3.6mg/dl confirming acquired angioedema. Ultimately, bone marrow biopsy and cytogenetic analysis confirmed splenic marginal zone B-cell lymphoma. The patient was started on rituximab, her fatigue improved, and her c1 esterase inhibitor quantitative and qualitative levels normalized. Since