Age: 38.0
Sex: F
Vaccine: COVID19
Symptoms: Complement factor C4, Condition aggravated, Hereditary angioedema with normal C1 esterase inhibitor, Laboratory test, Physical examination
Clinical narrative: Hereditary angioedema with normal C1 esterase inhibitor; Hereditary angioedema with normal C1 esterase inhibitor; Anaphylactic reaction; This literature-non-study case was reported in a literature article and describes the occurrence of HEREDITARY ANGIOEDEMA WITH NORMAL C1 ESTERASE INHIBITOR (Hereditary angioedema with normal C1 esterase inhibitor), CONDITION AGGRAVATED (Hereditary angioedema with normal C1 esterase inhibitor) and ANAPHYLACTIC REACTION (Anaphylactic reaction) in a 38-year-old female patient who received mRNA-1273 (Moderna COVID-19 Vaccine) for COVID-19 prophylaxis.      The patient's past medical history included Angioedema (Started at age of 16 years). Previously administered products included for Drug use for unknown indication: lidocaine (angioedema flares attributed to receiving lidocaine injections). Past adverse reactions to the above products included Angioedema aggravated with lidocaine. Family history included Idiopathic angioedema (pertinent in both her mother and grandmother which lead to passing of her mother) since an unknown date. Concurrent medical conditions included Fruit allergy (angioedema flares attributed to eating mango).    In 2020, the patient received first dose of mRNA-1273 (Moderna COVID-19 Vaccine) (unknown route) 1 dosage form. In 2020, the patient experienced HEREDITARY ANGIOEDEMA WITH NORMAL C1 ESTERASE INHIBITOR (Hereditary angioedema with normal C1 esterase inhibitor) (seriousness criteria hospitalization, disability and medically significant), CONDITION AGGRAVATED (Hereditary angioedema with normal C1 esterase inhibitor) (seriousness criteria hospitalization, disability and medically significant) and ANAPHYLACTIC REACTION (Anaphylactic reaction) (seriousness criteria hospitalization, disability and medically significant). The patient was hospitalized on sometime in 2020 due to ANAPHYLACTIC REACTION, CONDITION AGGRAVATED and HEREDITARY ANGIOEDEMA WITH NORMAL C1 ESTERASE INHIBITOR. The patient was treated with CONESTAT ALFA (RUCONEST) (intravenous) in 2020 at an unspecified dose and frequency; ICATIBANT ACETATE (FIRAZYR) (subcutaneous) in 2020 at an unspecified dose and frequency; BEROTRALSTAT DIHYDROCHLORIDE (ORLADEYO) (oral) for Prophylaxis, at an unspecified dose and frequency; FAMOTIDINE (PEPCID [FAMOTIDINE]) at an unspecified dose and frequency; DIPHENHYDRAMINE HYDROCHLORIDE (BENADRYL [DIPHENHYDRAMINE HYDROCHLORIDE]) at an unspecified dose and frequency; COMPLEMENT C1 ESTERASE INHIBITOR (BERINERT) (intravenous) at an unspecified dose and frequency; COMPLEMENT C1 ESTERASE INHIBITOR (HAEGARDA) (subcutaneous) for Prophylaxis, at an unspecified dose and frequency and LANADELUMAB (TAKHZYRO [LANADELUMAB]) (subcutaneous) for Prophylaxis, at an unspecified dose and frequency. At the time of the report, HEREDITARY ANGIOEDEMA WITH NORMAL C1 ESTERASE INHIBITOR (Hereditary angioedema with normal C1 esterase inhibitor), CONDITION AGGRAVATED (Hereditary angioedema with normal C1 esterase inhibitor) and ANAPHYLACTIC REACTION (Anaphylactic reaction) outcome was unknown.      DIAGNOSTIC RESULTS (normal ranges are provided in parenthesis if available): In 2020, Blood immunoglobulin E: less than 0.10 kU/L Normal. In 2020, C1 esterase inhibitor test (19-37 mg/dl): 41 mg/dl Normal and Greater than 91%( Normal range was greater than 67%)  Normal. In 2020, Complement factor C1 (12-22 mg/dl): 19 mg/dl Normal. In 2020, Complement factor C3 (88-200 mg/dl): 149 mg/dl Normal. In 2020, Complement factor C4 (10-49 mg/dl): 42 mg/dl Normal. In 2020, Laboratory test: No pathogenic mutations found for ANGPT1: Angiopoietin 1; F12: Coagulation Factor XII; SERPING1: Serpin Family G Member 1; PLG: Plasminogen1. In 2020, Physical examination: positive for hoarseness, right upper lid swelling with visual impairment, and tongue swelling.     The action taken with mRNA-1273 (Moderna COVID-19 Vaccine) (Unknown) was unknown.   For mRNA-1273 (Moderna COVID-19 Vaccine) (Unknown), the reporter did not provide any causality assessments.   Patient had history of angioedema flares that were attributed to taking angiotensin receptor blockers, receiving lidocaine injections, and eating mango. Concomitant medications were not provided.  In 2020, the patient received her first vaccine for SARS-CoV-2, (COVID-19 mRNA vaccine), which was followed by an anaphylactic reaction and required admission to the intensive care unit (ICU). Following that incident, the patient experienced frequent, severe attacks that prompted her first consultation with an outpatient allergy clinic. The working diagnosis of HAE nC1-INH was entertained as her C1 esterase inhibitor level, C1 esterase inhibitor function, and C1q were normal. Galactose-alpha-1,3-galactose IgE test result was <0.10 kU/L (normal range:  <0.10 kU/L). Hereditary angioedema panel screening revealed no pathogenic mutations (Angiopoietin 1, Coagulation Factor XII, Serpin Family G Member 1 and Plasminogen). This treatment regimen reduced symptoms for a few days, after which she returned to the hospital for a severe laryngeal swell and was admitted to the ICU. Due to a lack of on-demand HAE medication availability, she was intubated and given glucocorticoids, Pepcid, Benadryl, Berinert and fresh frozen plasma. The patient continued to have episodes of angioedema, leading to several emergency department visits. Sajazir was added for on-demand therapy. The patient continued these treatments for several months. Although the severity of the symptoms had attenuated, the patient continued to have episodes of significant angioedema, including one additional hospitalization. The role of estrogen has been well documented as a factor in HAE nC1-INH exacerbations. The patient was on a trial of Danazol, an anabolic androgen. She also consulted with an obstetrician and gynecologist about a possible oophorectomy. The patient's quality of life has been severely affected, and a short-term disability has been obtained.  Company Comment: This is a literature non-study case concerning a 38-year-old, female patient with a past medical history of Angioedema (Started at age of 16 years), family history of Idiopathic angioedema (in both her mother and grandmother which lead to passing of her mother) and angioedema flares secondary to angiotensin receptor blockers, lidocaine injections, and eating mango, who experienced the serious (due to medically significant  disability  hospitalization) unexpected events of Hereditary angioedema with normal C1 esterase inhibitor, Hereditary angioedema with normal C1 esterase inhibitor condition aggravated (exacerbations) and the expected event of Anaphylactic reaction. The patient experienced the event of anaphylactic reaction after the first dose of mRNA-1273 and required admission to the intensive care unit. After that, she subsequently experienced frequent, severe attacks that led to ER visits including one intubation and two hospitalizations. The symptoms presented at clinical exam included hoarseness, right upper lid swelling with visual impairment, and tongue swelling. Laboratory tests performed included Hereditary angioedema laboratory panel (Complement C4, Complement C3, Complement C1q, C1 esterase inhibitor function, C1 esterase inhibitor and Galactose-alpha-1,3 galactose IgE) within normal values. The patient was also screened genetically via the Hereditary Angioedema Panel (Angiopoietin 1; Coagulation Factor XII; Serpin Family G Member 1; Plasminogen), and no pathogenic mutations were found. Treatment patient received included an intravenous recombinant C1 esterase inhibitor, subcutaneous bradykinin B2 receptor antagonist, oral kallikrein inhibitor, glucocorticoids, H2 antagonist, H1 antagonist, an intravenous plasma-derived C1 esterase inhibitor, fresh frozen plasma, a subcutaneous plasma-derived C1 esterase inhibitor, a subcutaneous kallikrein inhibitor and subcutaneous bradykinin B2 receptor antagonist. The outcome of the events was reported as unknown. The mentioned medical history of angioedema, and family history of idiopatic angioedema remains as confounders. The event Hereditary angioedema with normal C1 esterase inhibitor could also be triggered by patient´s estrogen levels. The benefit-risk relationship of mRNA-1273 vaccine is not affected by this report.; Sender's Comments: Company Comment: This is a literature non-study case concerning a 38-year-old, female patient with a past medical history of Angioedema (Started at age of 16 years), family history of Idiopathic angioedema (in both her mother and grandmother which lead to passing of her mother) and angioedema flares secondary to angiotensin receptor blockers, lidocaine injections, and eating mango, who experienced the serious (due to medically significant  disability  hospitalization) unexpected events of Hereditary angioedema with normal C1 esterase inhibitor, Hereditary angioedema with normal C1 esterase inhibitor condition aggravated (exacerbations) and the expected event of Anaphylactic reaction. The patient experienced the event of anaphylactic reaction after the first dose of mRNA-1273 and required admission to the intensive care unit. After that, she subsequently experienced frequent, severe attacks that led to ER visits including one intubation and two hospitalizations. The symptoms presented at clinical exam included hoarseness, right upper lid swelling with visual impairment, and tongue swelling. Laboratory tests performed included Hereditary angioedema laboratory panel (Complement C4, Complement C3, Complement C1q, C1 esterase inhibitor function, C1 esterase inhibitor and Galactose-alpha-1,3 galactose IgE) within normal values. The patient was also screened genetically via the Hereditary Angioedema Panel (Angiopoietin 1; Coagulation Factor XII; Serpin Family G Member 1; Plasminogen), and no pathogenic mutations were found. Treatment patient received included an intravenous recombinant C1 esterase inhibitor, subcutaneous bradykinin B2 receptor antagonist, oral kallikrein inhibitor, glucocorticoids, H2 antagonist, H1 antagonist, an intravenous plasma-derived C1 esterase inhibitor, fresh frozen plasma, a subcutaneous plasma-derived C1 esterase inhibitor, a subcutaneous kallikrein inhibitor and subcutaneous bradykinin B2 receptor antagonist. The outcome of the events was reported as unknown. The mentioned medical history of angioedema, and family history of idiopatic angioedema remains as confounders. The event Hereditary angioedema with normal C1 esterase inhibitor could also be triggered by patient´s estrogen levels. The benefit-risk relationship of mRNA-1273 vaccine is not affected by this report.