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P099 Acute angioedema associated with iron deficiency anemia
S50
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 117 (2016) S22eS124
Results: Thirty two patients were included, 78% were women. The most common type of HAE was Type I (41%). In 1 year, 32% of patients present 2-3 attacks per month. The most common locations were: abdomen, face, peripheral limbs and upper airway. Fifty-three percent of patients were using prophylaxis therapy; C1 esterase inhibitor being the most common. Eighty-one percent of patients were using rescue mediation; Icatibant being the most common. Areas with significant burden were pain and vitality followed by mental health, activities of daily living and social aspect with lesser impairment in physical function and general health. Conclusion: Patients in our study differ in clinical characteristics as compared to previous study done in 2004. Impaired quality of life was noted. The most affected areas were those related to pain and vitality. Management of HAE patients should be optimized to improve quality of life.
P097 CEREBRAL VENOUS THROMBOSIS, A MASQUERADER OF ANGIOEDEMA IN A PEDIATRIC PATIENT J. Toh*1, Y. Lee2, L. Bernstein3, 1. New York, NY; 2. Bronx, NY; 3. Fresh Meadows, NY. Introduction: It is important for Allergists to recognize the differential diagnosis of facial angioedema including masqueraders such as Melkersson-Rosenthal syndrome, myxedema, superior vena cava syndrome and infection. Some may be life-threatening and it is important to recognize them early. We present a pediatric case of facial swelling caused by underlying cerebral venous thrombosis. Methods: Case report Results: A 14-year-old girl presented with a one-day history of worsening lip and bilateral periocular swelling with mild pruritus. Our allergy service was consulted for possible angioedema. One day prior to presentation, she went to another emergency room for treatment after being elbowed in the face and was given ibuprofen and pseudoephedrine which she took later that evening. Exam and laboratory values were notable for a fever (Tmax 102.4F), severe bilateral periorbital edema extending to the forehead, and leukocytosis with bandemia (WBC 11.5 k/uL, 20% bands). She was treated with IV clindamycin, ceftriaxone, antihistamines, and prednisone for soft tissue infection with suspected concurrent angioedema secondary to NSAIDs. However, the swelling progressed, she developed meningeal signs and blood cultures were positive for methicillin-sensitive S.aureus. An MRI revealed cellulitis of the orbits and thrombosis of the superior ophthalmic veins, cavernous sinuses and scalp veins. Antibiotic coverage was broadened, anticoagulation was added, antihistamines were discontinued and she was switched to dexamethasone. Conclusion: Allergists should be aware of the broad differential diagnosis of angioedema including life-threatening conditions such as venous thrombosis. It is imperative that a good history, physical and labs be performed to aid in proper diagnosis and management.
P098 WHEN POST-OPERATIVE OROFACIAL ANGIOEDEMA IS NOT IGE OR COMPLEMENT-MEDIATED? C. Yeh, A. Kourosh, J. Ongkasuwan, A. Ramirez, D. Bashir, I. Hanson, Houston, TX. Introduction: Post-operative orofacial angioedema with or without anaphylaxis is well described in the literature and the differential diagnosis is broad. We present a case of post-operative orofacial edema due to sialadenitis. Methods: Medical record and literature review were conducted. Results: A 16 year old Hispanic female with an intractable seizure disorder presented with acute onset of right sided facial swelling immediately following an uneventful 10 hour left temporal lobe
resection. In the recovery room, she developed painful right sided facial and neck swelling, vocal fold and brachial plexus weakness, and airway obstruction requiring re-intubation. Urticaria, hypotension and wheezing were absent. She did not have a past history of edema with trauma nor did she have a family history of angioedema. An emergent ultrasound and CT neck were performed to rule out post-operative hematoma. These revealed an edema of the right sternoclidomastoid muscle and submandibular gland concerning for sialadenitis. Serum tryptase, complement C4 level, C1 esterase inhibitor level and function studies were normal. The edema did not respond to initial epinephrine, antihistamines or steroids and continued to progress over the following days. She received C1 esterase inhibitor protein without improvement. Rhabdomyolisis was documented with elevation of serum CK, urine myoglobulin, and transaminases which we theorize resulted in a chemical myositis from outpouring of salivary enzymes from an obstructive salivary gland. Following hydration and antibiotic treatment her condition normalized. Conclusion: Post-operative angioedema is frequently mediated by tryptase or bradykinin tissue effect. Sialadenitis should be included in the non-IgE/complement driven differential diagnosis of postoperative facial edema.
Post-operative right side orofacial edema
P099 ACUTE ANGIOEDEMA ASSOCIATED WITH IRON DEFICIENCY ANEMIA J. Bay*, C. Mikita, Bethesda, MD. Introduction: Acute angioedema with or without urticaria is a selflimiting condition that can occur in up to 20 percent of the general population at some point during their lifetime. In the absence of a history of hereditary or acquired angioedema, ACE-inhibitor use or autoimmune disease, many cases are considered idiopathic in etiology. We present two patients who developed severe acute angioedema in the setting of iron deficiency anemia. Methods: Clinical exams, laboratory evaluation. Results: Two otherwise healthy, young females presented to the emergency department with acute onset severe angioedema of the lips and tongue without associated urticaria. Both patients received H1 and H2 antagonists and intravenous steroids with resolution of their symptoms. On further evaluation, both patients were found to have new onset iron deficiency anemia concurrent with their episode with no other laboratory abnormalities or significant past medical history. After starting oral iron supplementation, both patients’ anemia resolved and angioedema did not recur during a 9month follow-up period. Conclusion: Iron deficiency anemia has been reported to be associated with the development of chronic urticaria. Murine models have suggested the mechanism involves reduced inhibition of histamine release by iron binding proteins. Iron deficiency anemia as a potential trigger for isolated angioedema has not been
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 117 (2016) S22eS124
S51
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
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 117 (2016) S22eS124
Results: Thirty two patients were included, 78% were women. The most common type of HAE was Type I (41%). In 1 year, 32% of patients present 2-3 attacks per month. The most common locations were: abdomen, face, peripheral limbs and upper airway. Fifty-three percent of patients were using prophylaxis therapy; C1 esterase inhibitor being the most common. Eighty-one percent of patients were using rescue mediation; Icatibant being the most common. Areas with significant burden were pain and vitality followed by mental health, activities of daily living and social aspect with lesser impairment in physical function and general health. Conclusion: Patients in our study differ in clinical characteristics as compared to previous study done in 2004. Impaired quality of life was noted. The most affected areas were those related to pain and vitality. Management of HAE patients should be optimized to improve quality of life.
P097 CEREBRAL VENOUS THROMBOSIS, A MASQUERADER OF ANGIOEDEMA IN A PEDIATRIC PATIENT J. Toh*1, Y. Lee2, L. Bernstein3, 1. New York, NY; 2. Bronx, NY; 3. Fresh Meadows, NY. Introduction: It is important for Allergists to recognize the differential diagnosis of facial angioedema including masqueraders such as Melkersson-Rosenthal syndrome, myxedema, superior vena cava syndrome and infection. Some may be life-threatening and it is important to recognize them early. We present a pediatric case of facial swelling caused by underlying cerebral venous thrombosis. Methods: Case report Results: A 14-year-old girl presented with a one-day history of worsening lip and bilateral periocular swelling with mild pruritus. Our allergy service was consulted for possible angioedema. One day prior to presentation, she went to another emergency room for treatment after being elbowed in the face and was given ibuprofen and pseudoephedrine which she took later that evening. Exam and laboratory values were notable for a fever (Tmax 102.4F), severe bilateral periorbital edema extending to the forehead, and leukocytosis with bandemia (WBC 11.5 k/uL, 20% bands). She was treated with IV clindamycin, ceftriaxone, antihistamines, and prednisone for soft tissue infection with suspected concurrent angioedema secondary to NSAIDs. However, the swelling progressed, she developed meningeal signs and blood cultures were positive for methicillin-sensitive S.aureus. An MRI revealed cellulitis of the orbits and thrombosis of the superior ophthalmic veins, cavernous sinuses and scalp veins. Antibiotic coverage was broadened, anticoagulation was added, antihistamines were discontinued and she was switched to dexamethasone. Conclusion: Allergists should be aware of the broad differential diagnosis of angioedema including life-threatening conditions such as venous thrombosis. It is imperative that a good history, physical and labs be performed to aid in proper diagnosis and management.
P098 WHEN POST-OPERATIVE OROFACIAL ANGIOEDEMA IS NOT IGE OR COMPLEMENT-MEDIATED? C. Yeh, A. Kourosh, J. Ongkasuwan, A. Ramirez, D. Bashir, I. Hanson, Houston, TX. Introduction: Post-operative orofacial angioedema with or without anaphylaxis is well described in the literature and the differential diagnosis is broad. We present a case of post-operative orofacial edema due to sialadenitis. Methods: Medical record and literature review were conducted. Results: A 16 year old Hispanic female with an intractable seizure disorder presented with acute onset of right sided facial swelling immediately following an uneventful 10 hour left temporal lobe
resection. In the recovery room, she developed painful right sided facial and neck swelling, vocal fold and brachial plexus weakness, and airway obstruction requiring re-intubation. Urticaria, hypotension and wheezing were absent. She did not have a past history of edema with trauma nor did she have a family history of angioedema. An emergent ultrasound and CT neck were performed to rule out post-operative hematoma. These revealed an edema of the right sternoclidomastoid muscle and submandibular gland concerning for sialadenitis. Serum tryptase, complement C4 level, C1 esterase inhibitor level and function studies were normal. The edema did not respond to initial epinephrine, antihistamines or steroids and continued to progress over the following days. She received C1 esterase inhibitor protein without improvement. Rhabdomyolisis was documented with elevation of serum CK, urine myoglobulin, and transaminases which we theorize resulted in a chemical myositis from outpouring of salivary enzymes from an obstructive salivary gland. Following hydration and antibiotic treatment her condition normalized. Conclusion: Post-operative angioedema is frequently mediated by tryptase or bradykinin tissue effect. Sialadenitis should be included in the non-IgE/complement driven differential diagnosis of postoperative facial edema.
Post-operative right side orofacial edema
P099 ACUTE ANGIOEDEMA ASSOCIATED WITH IRON DEFICIENCY ANEMIA J. Bay*, C. Mikita, Bethesda, MD. Introduction: Acute angioedema with or without urticaria is a selflimiting condition that can occur in up to 20 percent of the general population at some point during their lifetime. In the absence of a history of hereditary or acquired angioedema, ACE-inhibitor use or autoimmune disease, many cases are considered idiopathic in etiology. We present two patients who developed severe acute angioedema in the setting of iron deficiency anemia. Methods: Clinical exams, laboratory evaluation. Results: Two otherwise healthy, young females presented to the emergency department with acute onset severe angioedema of the lips and tongue without associated urticaria. Both patients received H1 and H2 antagonists and intravenous steroids with resolution of their symptoms. On further evaluation, both patients were found to have new onset iron deficiency anemia concurrent with their episode with no other laboratory abnormalities or significant past medical history. After starting oral iron supplementation, both patients’ anemia resolved and angioedema did not recur during a 9month follow-up period. Conclusion: Iron deficiency anemia has been reported to be associated with the development of chronic urticaria. Murine models have suggested the mechanism involves reduced inhibition of histamine release by iron binding proteins. Iron deficiency anemia as a potential trigger for isolated angioedema has not been
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 117 (2016) S22eS124
S51
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