Patient Presentation
A 58-year-old man presented to the emergency department complaining of facial edema. The swelling had begun acutely 24 hours prior to presentation. The edema was initially more prominent on the right side, but progressed over 12 hours to involve the entire face. He denied pain or pruritus associated with the swelling. He denied shortness of breath, difficulty swallowing or breathing, changes to his voice, abdominal pain, nausea, vomiting, or rash.
The patient’s past medical history was significant for hypertension, coronary artery disease with stenting, as well as a recent history of cellulitis of the lower right extremity that had resolved after several days. His family history was non-contributory. His only medication was Lopressor 50 mg daily.
On physical examination, the patient had a marked edema of his lower face and lips without erythema, tenderness, or crepitus on palpation. His breath sounds were full and equal with no stridor. He had no associated urticaria. His physical exam was otherwise unremarkable. His complete blood cell count, coagulation panel and basic metabolic panel were normal.Discussion
There are many types of angioedema, including drug-induced, allergic, idiopathic, infection-related, hereditary, and acquired. Our case depicts an example of an acquired angioedema.
What’s Your Diagnosis?
Diagnosis: Acquired Angioedema
Discussion
There are many types of angioedema, including drug-induced, allergic, idiopathic, infection-related, hereditary, and acquired. Our case depicts an example of an acquired angioedema.Acquired angioedema (AAE) is a rare disorder characterized by the acute development of non-pruritic, non-tender subcutaneous edema most commonly manifesting on the face, larynx, genitals, or gastrointestinal tract. It was first described in 1972 in association with lymphoproliferative disorders, and has since been subdivided into two types based on its pathogenesis.1
Type I AAE is associated with an underlying lymphoproliferative process.
Type II AAE is described as an autoimmune connective tissue disease defined by the presence of autoantibodies to C1 esterase inhibitor.1,2
Epidemiology
Type I AAE is a rare disease that usually presents in the fourth to fifth decade of life. At this time, fewer than 100 cases have been reported in the literature, making diagnosis and treatment parameters difficult to define.3 Patients may, at presentation, have a diagnosis of a lymphoproliferative disorder or may be at an increased risk of developing one, especially a B-cell malignancy.3
Specific diseases associated with the development of AAE are vast and include monoclonal gammopathy of undetermined significance, multiple myeloma, Walden-strom’s macroglobulinemia, B-cell lymphomas, and chronic lymphocytic leukemia, as well as non-hematologic malignancies, infections, and autoimmune diseases.3
Pathogenesis
Patients with AAE have a C1-inhibitor (C1-INH) deficiency. C1-INH is a member of protease inhibitors known as the serpin family and acts as a suicide inhibitor. The substrates of C1-INH are broad, which makes the exact mechanism of AAE difficult to isolate. C1-INH has been implicated in the control of the classical complement pathway (via inactivation of C1r and C1s),4 the alternative complement pathway (via binding to C3b),5 and the contact coagulation pathway (via the inactivation of the Hageman factor and kallikrein, causing a decrease of bradykinin production),6 as well as others.7,8 Thus, a decrease in the action of the C1-inhibitor results in unchecked activation of the complement pathways and increased bradykinin production, both of which have been implicated in the production of angioedema.7,9
In Type I AAE, a lymphoproliferative state produces idiotype-anti-idiotype immune complexes causing excessive activation of the complement system and leading to consumption of C1-INH.7
In contrast, Type II AAE is due to autoantibodies directed to the C1 inhibitor, which block the action of C1-INH, effectively eliminating its functionality.10 More recently, studies in the literature suggest that the distinctions between Type I and Type II AAE are not definite.3
Clinical Features
Patients with AAE Type I or II usually present in middle age with episodes of angioedema of the head, extremities, genitalia, respiratory tract, or gastrointestinal tract, in the absence of a family history of angioedema. Most patients describe acute onset of attacks that are localized and usually last less than 48 hours.7
The lesions are non-pruritic, non-tender, and are well-demarcated, and due to the absence of symptoms, patients may not seek medical attention for the initial lesions. Episodes can occur at intervals ranging from 1 to 9 months and vary in severity, duration, and location from patient to patient.7
Angioedema of the upper airway is the greatest source of mortality for AAE patients and may be severe enough to require emergency surgical intervention, including tracheostomy. Symptoms suggestive of upper airway involvement include stridor, dysphagia, and an alteration in the voice.3 Symptoms involving the gastrointestinal tract present as colicky abdominal pain and possibly vomiting, which may be misdiagnosed initially as irritable bowel syndrome.7
Differential Diagnosis
The differential diagnosis for angioedema includes allergic causes, drug-induced angioedema, hereditary angioedema (HAE), and AAE. Clinically, these disorders resemble one another, but can be differentiated based on history and response to treatment.
In general, allergic angioedema has coincident urticaria, and because it is histamine-mediated, it responds to therapy with antihistamines and steroids.
Drug-induced angioedema has been associated with multiple agents that are widely used in practice and include (but are not limited to) non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors (ACE inhibitors), and estrogens.11 These patients will respond to cessation of the offending agent.
When HAE or AAE are suspected, initial screening labs should include C3 and C4 levels. HAE can be differentiated from AAE in several ways. HAE usually presents in younger patients who have a family history of angioedema; additionally, HAE patients will have normal C1q laboratory levels in contrast to the decreased levels seen in AAE.7,12
Laboratory Investigations
The diagnosis of AAE is made by clinical evidence in conjunction with laboratory values that suggest depleted complement components with qualitative and functional analysis of C1-INH.
Initial screening labs should include C3 and C4 levels. Normal C3 levels in the presence of low C4 should prompt further investigation, but are not sufficient to make a diagnosis since depleted C4 levels can be seen in other disorders, including mixed connective tissue diseases.13
Next, a C1q level should be obtained; if low, this suggests AAE (a normal C1q at this point would support a diagnosis of HAE).7
Further testing may include C1-INH protein levels and C1-INH function to distinguish between Type I and Type II AAE. In Type I AAE, immune complexes fix the complement and result in the consumption of C1-INH protein. As a result, C1-INH protein is low but functional, so measurements of protein levels and function are proportionately low. This is in contrast to Type II AAE, in which antibodies to C1-INH cause a functional impairment of the enzyme, so that laboratory values reflect normal levels of C1-INH protein, but diminished function.7,14 Alternatively, immunoblotting can be used to identify an antibody to C1-INH and confirm a diagnosis of Type II AAE.13
In light of the association between AAE and lymphoproliferative disorders, once a diagnosis of AAE has been made, investigational testing should be performed. A thorough work-up to rule out an associated lymphoproliferative disease should include serum protein electrophoresis, computed tomography of the chest, abdomen, and pelvis, and possibly a bone marrow biopsy.7 In addition, if Type II AAE is clinically suspected, serology such as RF, ANA, ESR, and CRP should be ordered to rule out an associated connective tissue disease.
Treatment
Treatment of AAE should focus on the management of acute attacks of angioedema and long-term prophylaxis. The importance of rapid, effective treatment for acute attacks is highlighted by the potential morbidity and mortality associated with laryngeal edema.
For patients in the acute setting, C1-INH concentrate or fresh-frozen plasma has been shown effective, although most of the data is based on patients with HAE.3,15
For long-term prophylaxis of attacks, Type I AAE patients may respond to treatment of the underlying myelodysplastic disease.3
However, for Type II AAE patients or Type I patients who do not respond to disease remission, prophylaxis may be obtained with attenuated androgens (danazol or stanozolol) or anti-fibrinolytic agents (tranexamic acid).3,7,14 While attenuated androgens have been the mainstay of therapy, Cicardi et al recommend the use of tranexamic acid as the first-line agent for prophylaxis in AAE patients.3
For patients with mild disease, it is reasonable to take a conservative approach and treat only acute flares. Additionally, patients should be educated about the signs of laryngeal edema, and in general, these patients are advised to avoid ACE inhibitors, which trigger drug-induced angioedema.7 Future therapy may include agents that block the development of bradykinin, which is thought to be a major contributor to angioedema.7
Prognosis
In general, patients with acquired angioedema fare well. Major sources of mortality arise from cases of laryngeal edema or are secondary to the malignancies that underlie AAE Type I. However, morbidity can be significant, given that these patients are often misdiagnosed or undiagnosed for an average of 2 years.7
Because prophylactic treatment is generally well-tolerated and effective, earlier diagnosis of AAE patients can prevent years of symptomatology and unnecessary medical interventions.
Patient Presentation
A 58-year-old man presented to the emergency department complaining of facial edema. The swelling had begun acutely 24 hours prior to presentation. The edema was initially more prominent on the right side, but progressed over 12 hours to involve the entire face. He denied pain or pruritus associated with the swelling. He denied shortness of breath, difficulty swallowing or breathing, changes to his voice, abdominal pain, nausea, vomiting, or rash.
The patient’s past medical history was significant for hypertension, coronary artery disease with stenting, as well as a recent history of cellulitis of the lower right extremity that had resolved after several days. His family history was non-contributory. His only medication was Lopressor 50 mg daily.
On physical examination, the patient had a marked edema of his lower face and lips without erythema, tenderness, or crepitus on palpation. His breath sounds were full and equal with no stridor. He had no associated urticaria. His physical exam was otherwise unremarkable. His complete blood cell count, coagulation panel and basic metabolic panel were normal.Discussion
There are many types of angioedema, including drug-induced, allergic, idiopathic, infection-related, hereditary, and acquired. Our case depicts an example of an acquired angioedema.
What’s Your Diagnosis?
Diagnosis: Acquired Angioedema
Discussion
There are many types of angioedema, including drug-induced, allergic, idiopathic, infection-related, hereditary, and acquired. Our case depicts an example of an acquired angioedema.Acquired angioedema (AAE) is a rare disorder characterized by the acute development of non-pruritic, non-tender subcutaneous edema most commonly manifesting on the face, larynx, genitals, or gastrointestinal tract. It was first described in 1972 in association with lymphoproliferative disorders, and has since been subdivided into two types based on its pathogenesis.1
Type I AAE is associated with an underlying lymphoproliferative process.
Type II AAE is described as an autoimmune connective tissue disease defined by the presence of autoantibodies to C1 esterase inhibitor.1,2
Epidemiology
Type I AAE is a rare disease that usually presents in the fourth to fifth decade of life. At this time, fewer than 100 cases have been reported in the literature, making diagnosis and treatment parameters difficult to define.3 Patients may, at presentation, have a diagnosis of a lymphoproliferative disorder or may be at an increased risk of developing one, especially a B-cell malignancy.3
Specific diseases associated with the development of AAE are vast and include monoclonal gammopathy of undetermined significance, multiple myeloma, Walden-strom’s macroglobulinemia, B-cell lymphomas, and chronic lymphocytic leukemia, as well as non-hematologic malignancies, infections, and autoimmune diseases.3
Pathogenesis
Patients with AAE have a C1-inhibitor (C1-INH) deficiency. C1-INH is a member of protease inhibitors known as the serpin family and acts as a suicide inhibitor. The substrates of C1-INH are broad, which makes the exact mechanism of AAE difficult to isolate. C1-INH has been implicated in the control of the classical complement pathway (via inactivation of C1r and C1s),4 the alternative complement pathway (via binding to C3b),5 and the contact coagulation pathway (via the inactivation of the Hageman factor and kallikrein, causing a decrease of bradykinin production),6 as well as others.7,8 Thus, a decrease in the action of the C1-inhibitor results in unchecked activation of the complement pathways and increased bradykinin production, both of which have been implicated in the production of angioedema.7,9
In Type I AAE, a lymphoproliferative state produces idiotype-anti-idiotype immune complexes causing excessive activation of the complement system and leading to consumption of C1-INH.7
In contrast, Type II AAE is due to autoantibodies directed to the C1 inhibitor, which block the action of C1-INH, effectively eliminating its functionality.10 More recently, studies in the literature suggest that the distinctions between Type I and Type II AAE are not definite.3
Clinical Features
Patients with AAE Type I or II usually present in middle age with episodes of angioedema of the head, extremities, genitalia, respiratory tract, or gastrointestinal tract, in the absence of a family history of angioedema. Most patients describe acute onset of attacks that are localized and usually last less than 48 hours.7
The lesions are non-pruritic, non-tender, and are well-demarcated, and due to the absence of symptoms, patients may not seek medical attention for the initial lesions. Episodes can occur at intervals ranging from 1 to 9 months and vary in severity, duration, and location from patient to patient.7
Angioedema of the upper airway is the greatest source of mortality for AAE patients and may be severe enough to require emergency surgical intervention, including tracheostomy. Symptoms suggestive of upper airway involvement include stridor, dysphagia, and an alteration in the voice.3 Symptoms involving the gastrointestinal tract present as colicky abdominal pain and possibly vomiting, which may be misdiagnosed initially as irritable bowel syndrome.7
Differential Diagnosis
The differential diagnosis for angioedema includes allergic causes, drug-induced angioedema, hereditary angioedema (HAE), and AAE. Clinically, these disorders resemble one another, but can be differentiated based on history and response to treatment.
In general, allergic angioedema has coincident urticaria, and because it is histamine-mediated, it responds to therapy with antihistamines and steroids.
Drug-induced angioedema has been associated with multiple agents that are widely used in practice and include (but are not limited to) non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors (ACE inhibitors), and estrogens.11 These patients will respond to cessation of the offending agent.
When HAE or AAE are suspected, initial screening labs should include C3 and C4 levels. HAE can be differentiated from AAE in several ways. HAE usually presents in younger patients who have a family history of angioedema; additionally, HAE patients will have normal C1q laboratory levels in contrast to the decreased levels seen in AAE.7,12
Laboratory Investigations
The diagnosis of AAE is made by clinical evidence in conjunction with laboratory values that suggest depleted complement components with qualitative and functional analysis of C1-INH.
Initial screening labs should include C3 and C4 levels. Normal C3 levels in the presence of low C4 should prompt further investigation, but are not sufficient to make a diagnosis since depleted C4 levels can be seen in other disorders, including mixed connective tissue diseases.13
Next, a C1q level should be obtained; if low, this suggests AAE (a normal C1q at this point would support a diagnosis of HAE).7
Further testing may include C1-INH protein levels and C1-INH function to distinguish between Type I and Type II AAE. In Type I AAE, immune complexes fix the complement and result in the consumption of C1-INH protein. As a result, C1-INH protein is low but functional, so measurements of protein levels and function are proportionately low. This is in contrast to Type II AAE, in which antibodies to C1-INH cause a functional impairment of the enzyme, so that laboratory values reflect normal levels of C1-INH protein, but diminished function.7,14 Alternatively, immunoblotting can be used to identify an antibody to C1-INH and confirm a diagnosis of Type II AAE.13
In light of the association between AAE and lymphoproliferative disorders, once a diagnosis of AAE has been made, investigational testing should be performed. A thorough work-up to rule out an associated lymphoproliferative disease should include serum protein electrophoresis, computed tomography of the chest, abdomen, and pelvis, and possibly a bone marrow biopsy.7 In addition, if Type II AAE is clinically suspected, serology such as RF, ANA, ESR, and CRP should be ordered to rule out an associated connective tissue disease.
Treatment
Treatment of AAE should focus on the management of acute attacks of angioedema and long-term prophylaxis. The importance of rapid, effective treatment for acute attacks is highlighted by the potential morbidity and mortality associated with laryngeal edema.
For patients in the acute setting, C1-INH concentrate or fresh-frozen plasma has been shown effective, although most of the data is based on patients with HAE.3,15
For long-term prophylaxis of attacks, Type I AAE patients may respond to treatment of the underlying myelodysplastic disease.3
However, for Type II AAE patients or Type I patients who do not respond to disease remission, prophylaxis may be obtained with attenuated androgens (danazol or stanozolol) or anti-fibrinolytic agents (tranexamic acid).3,7,14 While attenuated androgens have been the mainstay of therapy, Cicardi et al recommend the use of tranexamic acid as the first-line agent for prophylaxis in AAE patients.3
For patients with mild disease, it is reasonable to take a conservative approach and treat only acute flares. Additionally, patients should be educated about the signs of laryngeal edema, and in general, these patients are advised to avoid ACE inhibitors, which trigger drug-induced angioedema.7 Future therapy may include agents that block the development of bradykinin, which is thought to be a major contributor to angioedema.7
Prognosis
In general, patients with acquired angioedema fare well. Major sources of mortality arise from cases of laryngeal edema or are secondary to the malignancies that underlie AAE Type I. However, morbidity can be significant, given that these patients are often misdiagnosed or undiagnosed for an average of 2 years.7
Because prophylactic treatment is generally well-tolerated and effective, earlier diagnosis of AAE patients can prevent years of symptomatology and unnecessary medical interventions.
Patient Presentation
A 58-year-old man presented to the emergency department complaining of facial edema. The swelling had begun acutely 24 hours prior to presentation. The edema was initially more prominent on the right side, but progressed over 12 hours to involve the entire face. He denied pain or pruritus associated with the swelling. He denied shortness of breath, difficulty swallowing or breathing, changes to his voice, abdominal pain, nausea, vomiting, or rash.
The patient’s past medical history was significant for hypertension, coronary artery disease with stenting, as well as a recent history of cellulitis of the lower right extremity that had resolved after several days. His family history was non-contributory. His only medication was Lopressor 50 mg daily.
On physical examination, the patient had a marked edema of his lower face and lips without erythema, tenderness, or crepitus on palpation. His breath sounds were full and equal with no stridor. He had no associated urticaria. His physical exam was otherwise unremarkable. His complete blood cell count, coagulation panel and basic metabolic panel were normal.Discussion
There are many types of angioedema, including drug-induced, allergic, idiopathic, infection-related, hereditary, and acquired. Our case depicts an example of an acquired angioedema.
What’s Your Diagnosis?
Diagnosis: Acquired Angioedema
Discussion
There are many types of angioedema, including drug-induced, allergic, idiopathic, infection-related, hereditary, and acquired. Our case depicts an example of an acquired angioedema.Acquired angioedema (AAE) is a rare disorder characterized by the acute development of non-pruritic, non-tender subcutaneous edema most commonly manifesting on the face, larynx, genitals, or gastrointestinal tract. It was first described in 1972 in association with lymphoproliferative disorders, and has since been subdivided into two types based on its pathogenesis.1
Type I AAE is associated with an underlying lymphoproliferative process.
Type II AAE is described as an autoimmune connective tissue disease defined by the presence of autoantibodies to C1 esterase inhibitor.1,2
Epidemiology
Type I AAE is a rare disease that usually presents in the fourth to fifth decade of life. At this time, fewer than 100 cases have been reported in the literature, making diagnosis and treatment parameters difficult to define.3 Patients may, at presentation, have a diagnosis of a lymphoproliferative disorder or may be at an increased risk of developing one, especially a B-cell malignancy.3
Specific diseases associated with the development of AAE are vast and include monoclonal gammopathy of undetermined significance, multiple myeloma, Walden-strom’s macroglobulinemia, B-cell lymphomas, and chronic lymphocytic leukemia, as well as non-hematologic malignancies, infections, and autoimmune diseases.3
Pathogenesis
Patients with AAE have a C1-inhibitor (C1-INH) deficiency. C1-INH is a member of protease inhibitors known as the serpin family and acts as a suicide inhibitor. The substrates of C1-INH are broad, which makes the exact mechanism of AAE difficult to isolate. C1-INH has been implicated in the control of the classical complement pathway (via inactivation of C1r and C1s),4 the alternative complement pathway (via binding to C3b),5 and the contact coagulation pathway (via the inactivation of the Hageman factor and kallikrein, causing a decrease of bradykinin production),6 as well as others.7,8 Thus, a decrease in the action of the C1-inhibitor results in unchecked activation of the complement pathways and increased bradykinin production, both of which have been implicated in the production of angioedema.7,9
In Type I AAE, a lymphoproliferative state produces idiotype-anti-idiotype immune complexes causing excessive activation of the complement system and leading to consumption of C1-INH.7
In contrast, Type II AAE is due to autoantibodies directed to the C1 inhibitor, which block the action of C1-INH, effectively eliminating its functionality.10 More recently, studies in the literature suggest that the distinctions between Type I and Type II AAE are not definite.3
Clinical Features
Patients with AAE Type I or II usually present in middle age with episodes of angioedema of the head, extremities, genitalia, respiratory tract, or gastrointestinal tract, in the absence of a family history of angioedema. Most patients describe acute onset of attacks that are localized and usually last less than 48 hours.7
The lesions are non-pruritic, non-tender, and are well-demarcated, and due to the absence of symptoms, patients may not seek medical attention for the initial lesions. Episodes can occur at intervals ranging from 1 to 9 months and vary in severity, duration, and location from patient to patient.7
Angioedema of the upper airway is the greatest source of mortality for AAE patients and may be severe enough to require emergency surgical intervention, including tracheostomy. Symptoms suggestive of upper airway involvement include stridor, dysphagia, and an alteration in the voice.3 Symptoms involving the gastrointestinal tract present as colicky abdominal pain and possibly vomiting, which may be misdiagnosed initially as irritable bowel syndrome.7
Differential Diagnosis
The differential diagnosis for angioedema includes allergic causes, drug-induced angioedema, hereditary angioedema (HAE), and AAE. Clinically, these disorders resemble one another, but can be differentiated based on history and response to treatment.
In general, allergic angioedema has coincident urticaria, and because it is histamine-mediated, it responds to therapy with antihistamines and steroids.
Drug-induced angioedema has been associated with multiple agents that are widely used in practice and include (but are not limited to) non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors (ACE inhibitors), and estrogens.11 These patients will respond to cessation of the offending agent.
When HAE or AAE are suspected, initial screening labs should include C3 and C4 levels. HAE can be differentiated from AAE in several ways. HAE usually presents in younger patients who have a family history of angioedema; additionally, HAE patients will have normal C1q laboratory levels in contrast to the decreased levels seen in AAE.7,12
Laboratory Investigations
The diagnosis of AAE is made by clinical evidence in conjunction with laboratory values that suggest depleted complement components with qualitative and functional analysis of C1-INH.
Initial screening labs should include C3 and C4 levels. Normal C3 levels in the presence of low C4 should prompt further investigation, but are not sufficient to make a diagnosis since depleted C4 levels can be seen in other disorders, including mixed connective tissue diseases.13
Next, a C1q level should be obtained; if low, this suggests AAE (a normal C1q at this point would support a diagnosis of HAE).7
Further testing may include C1-INH protein levels and C1-INH function to distinguish between Type I and Type II AAE. In Type I AAE, immune complexes fix the complement and result in the consumption of C1-INH protein. As a result, C1-INH protein is low but functional, so measurements of protein levels and function are proportionately low. This is in contrast to Type II AAE, in which antibodies to C1-INH cause a functional impairment of the enzyme, so that laboratory values reflect normal levels of C1-INH protein, but diminished function.7,14 Alternatively, immunoblotting can be used to identify an antibody to C1-INH and confirm a diagnosis of Type II AAE.13
In light of the association between AAE and lymphoproliferative disorders, once a diagnosis of AAE has been made, investigational testing should be performed. A thorough work-up to rule out an associated lymphoproliferative disease should include serum protein electrophoresis, computed tomography of the chest, abdomen, and pelvis, and possibly a bone marrow biopsy.7 In addition, if Type II AAE is clinically suspected, serology such as RF, ANA, ESR, and CRP should be ordered to rule out an associated connective tissue disease.
Treatment
Treatment of AAE should focus on the management of acute attacks of angioedema and long-term prophylaxis. The importance of rapid, effective treatment for acute attacks is highlighted by the potential morbidity and mortality associated with laryngeal edema.
For patients in the acute setting, C1-INH concentrate or fresh-frozen plasma has been shown effective, although most of the data is based on patients with HAE.3,15
For long-term prophylaxis of attacks, Type I AAE patients may respond to treatment of the underlying myelodysplastic disease.3
However, for Type II AAE patients or Type I patients who do not respond to disease remission, prophylaxis may be obtained with attenuated androgens (danazol or stanozolol) or anti-fibrinolytic agents (tranexamic acid).3,7,14 While attenuated androgens have been the mainstay of therapy, Cicardi et al recommend the use of tranexamic acid as the first-line agent for prophylaxis in AAE patients.3
For patients with mild disease, it is reasonable to take a conservative approach and treat only acute flares. Additionally, patients should be educated about the signs of laryngeal edema, and in general, these patients are advised to avoid ACE inhibitors, which trigger drug-induced angioedema.7 Future therapy may include agents that block the development of bradykinin, which is thought to be a major contributor to angioedema.7
Prognosis
In general, patients with acquired angioedema fare well. Major sources of mortality arise from cases of laryngeal edema or are secondary to the malignancies that underlie AAE Type I. However, morbidity can be significant, given that these patients are often misdiagnosed or undiagnosed for an average of 2 years.7
Because prophylactic treatment is generally well-tolerated and effective, earlier diagnosis of AAE patients can prevent years of symptomatology and unnecessary medical interventions.
