Angioedema
Foreword A n g i o e d e m a : Wh a t We Kn o w a n d W h a t We N e e d t o K n o w
Rafeul Alam, MD, PhD Consulting Editor
Angioedema involving airways is a life-threatening condition, which is the cause of significant morbidity, emergency room visits, and hospitalizations. The economic impact of this condition is huge. There are two major forms of angioedema—bradykininmediated angioedema and histamine-mediated angioedema. The bradykinin-mediated angioedema is popularly known as the complement-mediated angioedema. It is now clear that bradykinin is the final mediator of this illness regardless of the functional status of the C1 esterase inhibitor SERPING1. This conclusion is supported by genetic manipulation studies in the mouse model and the efficacy of bradykinin inhibitors in angioedema. Bradykinin-mediated angioedema can be caused by a functional deficiency of SERPING1 (type 1 and 2 hereditary angioedema), which blocks kallikrein and factor XII, the Hageman factor—the upstream activators of bradykinin. It can also be caused by mutation of the Hageman factor (type 3 hereditary angioedema). Unfortunately, many patients do not fall into either category, so they are labeled with idiopathic angioedema, although bradykinin remains the final common mediator. Bradykinin-mediated angioedema responds to treatment with the C1 esterase inhibitor (fresh frozen plasma, concentrate, or recombinant C1 esterase inhibitor), kallikrein inhibitors, and bradykinin receptor antagonists. Prophylaxis with anabolic androgens and anti-fibrinolytics is helpful. This condition contrasts with histamine-mediated angioedema, which is frequently associated with urticaria, and represents a spectrum of the urticarial syndrome. Histamine-mediated angioedema is more common than bradykinin-mediated angioedema. It can be extrinsic (allergic/IgE mediated and nonallergic), autoimmune, and idiopathic. This form of angioedema responds to antihistamines, glucocorticoids, and epinephrine.
Supported by NIH Grants RO1 AI091614 and N01 HHSN272200700048C.
Immunol Allergy Clin N Am 33 (2013) ix–x http://dx.doi.org/10.1016/j.iac.2013.09.003 immunology.theclinics.com 0889-8561/13/$ – see front matter Ó 2013 Published by Elsevier Inc.
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Foreword
There are still many outstanding questions in the field of bradykinin-mediated angioedema. We need to know the mechanism of bradykinin generation in the idiopathic form of angioedema where the function of the C1 esterase inhibitor and the Hageman factor is normal. More importantly, we need a diagnostic test. We do not fully understand why C1 esterase inhibitor deficiency manifests with intermittent but not persistent angioedema. We also do not understand why patients with ACEinhibitor-induced angioedema continue to experience symptoms weeks and months after discontinuation of the ACE-inhibitor. To update us on the pathogenesis and management of this important disease, I have invited Dr Bruce Zuraw, a leading expert in the field, to edit this very exciting issue of the Immunology and Allergy Clinics of North America. Rafeul Alam, MD, PhD Division of Allergy and Immunology National Jewish Health and University of Colorado Denver 1400 Jackson Street Denver, CO 80206, USA E-mail address: [email protected]
Foreword A n g i o e d e m a : Wh a t We Kn o w a n d W h a t We N e e d t o K n o w
Rafeul Alam, MD, PhD Consulting Editor
Angioedema involving airways is a life-threatening condition, which is the cause of significant morbidity, emergency room visits, and hospitalizations. The economic impact of this condition is huge. There are two major forms of angioedema—bradykininmediated angioedema and histamine-mediated angioedema. The bradykinin-mediated angioedema is popularly known as the complement-mediated angioedema. It is now clear that bradykinin is the final mediator of this illness regardless of the functional status of the C1 esterase inhibitor SERPING1. This conclusion is supported by genetic manipulation studies in the mouse model and the efficacy of bradykinin inhibitors in angioedema. Bradykinin-mediated angioedema can be caused by a functional deficiency of SERPING1 (type 1 and 2 hereditary angioedema), which blocks kallikrein and factor XII, the Hageman factor—the upstream activators of bradykinin. It can also be caused by mutation of the Hageman factor (type 3 hereditary angioedema). Unfortunately, many patients do not fall into either category, so they are labeled with idiopathic angioedema, although bradykinin remains the final common mediator. Bradykinin-mediated angioedema responds to treatment with the C1 esterase inhibitor (fresh frozen plasma, concentrate, or recombinant C1 esterase inhibitor), kallikrein inhibitors, and bradykinin receptor antagonists. Prophylaxis with anabolic androgens and anti-fibrinolytics is helpful. This condition contrasts with histamine-mediated angioedema, which is frequently associated with urticaria, and represents a spectrum of the urticarial syndrome. Histamine-mediated angioedema is more common than bradykinin-mediated angioedema. It can be extrinsic (allergic/IgE mediated and nonallergic), autoimmune, and idiopathic. This form of angioedema responds to antihistamines, glucocorticoids, and epinephrine.
Supported by NIH Grants RO1 AI091614 and N01 HHSN272200700048C.
Immunol Allergy Clin N Am 33 (2013) ix–x http://dx.doi.org/10.1016/j.iac.2013.09.003 immunology.theclinics.com 0889-8561/13/$ – see front matter Ó 2013 Published by Elsevier Inc.
x
Foreword
There are still many outstanding questions in the field of bradykinin-mediated angioedema. We need to know the mechanism of bradykinin generation in the idiopathic form of angioedema where the function of the C1 esterase inhibitor and the Hageman factor is normal. More importantly, we need a diagnostic test. We do not fully understand why C1 esterase inhibitor deficiency manifests with intermittent but not persistent angioedema. We also do not understand why patients with ACEinhibitor-induced angioedema continue to experience symptoms weeks and months after discontinuation of the ACE-inhibitor. To update us on the pathogenesis and management of this important disease, I have invited Dr Bruce Zuraw, a leading expert in the field, to edit this very exciting issue of the Immunology and Allergy Clinics of North America. Rafeul Alam, MD, PhD Division of Allergy and Immunology National Jewish Health and University of Colorado Denver 1400 Jackson Street Denver, CO 80206, USA E-mail address: [email protected]
