Hereditary Angioedema
No Results
No Results
processing….
Although rare, hereditary angioedema (HAE) is associated with episodic attacks of edema formation that can have catastrophic consequences. Laryngeal edema can result in asphyxiation; abdominal angioedema attacks can lead to unnecessary surgery and delay in diagnosis, as well as to narcotic dependence due to severe pain; and cutaneous attacks can be disfiguring and disabling. [1]
Physical signs of HAE include overt, noninflammatory swelling of the skin and mucous membranes. They are referable to the following prominent sites:
Subcutaneous tissues: Face, hands, arms, legs, genitals, and buttocks
Abdominal organs: Stomach, intestines, bladder, and urethra; may manifest as vomiting, diarrhea, or paroxysmal colicky pain and can mimic a surgical emergency
Upper airway (larynx) and tongue: May result in laryngeal edema and upper airway obstruction
In approximately 25% of patients, erythema marginatum may precede the occurrence of edema. [4]
See Clinical Presentation for more detail.
Complement and genetic testing
The 3 types of HAE can be differentiated with complement testing and, in the case of HAE with normal C1 inhibitor levels, genetic testing. Type I HAE is characterized by the following:
Low C1 esterase inhibitor (C1-INH) protein level
Low C4 level
Normal C1q level
Type II HAE is characterized by the following:
Normal or elevated, but dysfunctional, C1-INH level
Low C4 level
Normal C1q level
HAE with normal C1 inhibitor levels is characterized by the following:
Normal C1-INH level
Normal C1-INH functional assay
Normal C4 and C1q level
Factor XII mutation may be present [5, 6]
Imaging studies
The following imaging studies can be used in the diagnosis of HAE:
Abdominal radiography: During attacks of gastrointestinal edema, features of ileus may be demonstrated
Chest radiography: Pleural effusions rarely may be seen
Abdominal ultrasonography or computed tomography scanning: Edematous thickening of the intestinal wall, a fluid layer around the bowel, and large amounts of free peritoneal fluid may be found
See Workup for more detail.
Agents used in the treatment of acute attacks of HAE include the following:
C1-INH concentrate: Berinert was approved in September 2009 by the US Food and Drug Administration (FDA) for the treatment of acute abdominal and facial angioedema attacks in adolescents and adults with HAE [7] ; in January 2012, an additional indication for Berinert, for laryngeal angioedema, was approved by the FDA; in July 2014, the FDA approved the recombinant human C1-INH (rhC1-INH) Ruconest to treat acute attacks of HAE in adolescents and adults, although its effectiveness was not established in patients with HAE that involve laryngeal attacks [2, 3]
Kallikrein inhibitor: During HAE attacks, unregulated plasma kallikrein activity results in excessive bradykinin generation, resulting in swelling; ecallantide (Kalbitor) is a recombinant agent that is a potent, selective, reversible kallikrein inhibitor; the FDA approved ecallantide in December 2009 for treating acute HAE attacks in patients aged 16 years and older [8]
Selective bradykinin B2 receptor antagonist: Icatibant (Firazyr) was approved by the FDA in 2011 for treatment of acute HAE attacks in adults [9, 10]
Prophylaxis
The Medical Advisory Board of the HAE Patient’s Association has recommended that patients be free to choose their preferred therapy. Prophylactic treatment includes attenuated androgens and the C1 inhibitor protein product Cinryze. If androgen therapy is used dosage should be minimized, balancing disease severity with minimizing adverse effects. The drug most commonly used is danazol, but all attenuated androgens are useful in treatment. The usual recommendation is to try to use 200 mg/day or less.
The nano-filtered C1-INH concentrate Cinryze was approved by the FDA in 2008 for HAE prophylaxis. It is reported to be effective in acute attacks, as well. [11] The first subcutaneous C1-INH concentrate (Haegarda) was approved by the FDA in June 2017 for HAE prophylaxis in adults and adolescents. [51] Lanadelumab, a monoclonal antibody that targets kallikrein, was approved for HAE prophylaxis in August 2018. [52]
See Treatment and Medication for more detail.
Hereditary angioedema (HAE) is an autosomal dominant disease caused by low levels of the plasma protein C1 inhibitor (C1-INH).
Deficiencies in C1-INH allow unchecked activation of the classic complement pathway and other biochemical systems including the bradykinin system. Patients can present with any combination of painless, nonpruritic, nonpitting swelling of the skin (cutaneous angioedema); severe abdominal pain; or acute airway obstruction.
There are 3 types of HAE. Type I HAE is defined by low plasma levels of a normal C1-INH protein reflecting an abnormality of one of the gene alleles of the protein. Type II HAE is characterized by the presence of normal or elevated levels of a dysfunctional C1-INH. Again, one of the two gene alleles is abnormal but here the allele leads to the release of a non-functional protein. HAE with normal C1 inhibitor was identified as an estrogen-dependent inherited form of angioedema occurring mainly in women with normal functional and quantitative levels of C1-INH. There is still no clear understanding of its pathophysiologic mechanism
Prior to the development of effective therapy, the mortality rate from HAE was 20-30%. Although preventable and treatable, the complications of this disease do not respond well to the usual therapies for angioedema; therefore, establishment of the correct diagnosis is critical. The most reliable and cost-effective screening test for HAE is a serum C4 level (see Workup).
Treatment of HAE consists of prophylaxis, management of acute attacks, and prophylactic therapy in situations where attacks may occur. In HAE types I and II, the treatment of choice in acute attacks consists of replacement with commercially available C1 inhibitor (C1-INH) concentrates [12] , a kallikrein inhibitor or a bradykinin receptor type 2 antagonist. If there is no specific treatment available, fresh-frozen plasma has been used, but the physician should understand that, because the plasma may supply the substrate for bradykinin generation, attacks can at times worsen before they improve.
At the time of this report there is no consensus on best therapy for HAE with normal C1 inhibitor (See Treatment.)
For a discussion of acquired angioedema, which is caused by a consumption of C1-INH for any of a number of reasons leading to low levels of this protein, see Acquired Angioedema. For a discussion of angioedema in children, see Pediatric Angioedema. Additionally, go to Angioedema and Emergent Treatment of Angioedema for complete information on these topics.
C1-INH is a member of the serpin family of protease inhibitors, as are alpha-antitrypsin, antithrombin III, and angiotensinogen. [13] These proteins stoichiometrically inactivate their target proteases by forming stable, one-to-one complexes with the protein to be inhibited.
Synthesized primarily by hepatocytes, C1-INH is also synthesized by monocytes. The regulation of the protein production is not completely understood but, since patients respond clinically to androgen therapy and demonstrate increased serum levels of C1-INH, it is believed that androgens may stimulate C1-INH synthesis. C1-INH also blocks activation of the lectin pathway by binding to mannose-binding lectin-associated serine proteases (MASPs).
Although named for its action on the first component of complement (C1 esterase), C1-INH also inhibits components of the fibrinolytic, clotting, and kinin pathways. Specifically, C1-INH inactivates plasmin-activated Hageman factor (factor XII), activated factor XI, plasma thromboplastin antecedent (PTA), and kallikrein.
Within the complement system, C1-INH blocks the activation of C1 and the rest of the classic complement pathway by binding to C1r and C1s. Without C1-INH, unchecked activation of C1, C2, and C4 occur before other inhibitors (C4-binding protein and factors H and I) can halt the cascade.
Evidence is now overwhelming that bradykinin is the mediator responsible for capillary leakage. [13] Researchers have demonstrated activation of the kinin system with increased blood bradykinin levels associated with clinical flares. Bradykinin is an important inflammatory mediator formed by the action of the plasma enzyme kallikrein on the substrate high molecular weight kininogen that causes neutrophil chemotaxis, capillary dilation with plasma leakage, and smooth muscle relaxation, and it has been linked to other forms of angioedema.
In an animal model of C1-INH deficiency, bradykinin and bradykinin receptor antagonists prevent capillary leakage. [14] The US Food and Drug Administration has approved the use of a kallikrein enzyme inhibitor for acute treatment, and a bradykinin type 2 receptor antagonist also terminates edema fluid generation and thus terminates attacks.
There is no question that a relatively small subgroup of patients with HAE with normal C1 inhibitor have a factor XII mutation and it is presumed that this mutation is of importance in initiation of attacks. This may be closely related to endothelial cell activation and the initiation of attacks but further research is clearly needed. [15, 16, 17]
Hereditary angioedema (HAE) is due to mutations within the C1-INH gene and is transmitted as an autosomal dominant trait. The gene for C1-INH (SERPING1) has been mapped to 11q12-q13.1.
Approximately 300 different genetic mutations have been described in HAE, and a spontaneous mutation rate of 25% has been reported. The 2 variants of HAE related to C1-INH function are type I (85%) and type II (15%).
Type I HAE is caused by mutations occurring throughout the gene, which result in either a truncated or misfolded protein. This protein is not secreted efficiently, resulting in low antigenic and functional plasma levels of a normal C1-INH protein. Even though one normal allele is present, less than 50% of functional C1-INH is present. A possible explanation is that the normal C1-INH protein is down-regulated, and this is supported by the finding of decreased levels of C1-INH mRNA in patients with HAE. [14] Since the C1 inhibitor binds to the protein it inactivates and the complex is removed from the circulation, this may also be responsible for the low levels of C1 inhibitor. Half the normal level of C1-INH is believed to be insufficient to prevent attacks of angioedema.
Most type II HAE is caused by mutations that involve the active site of exon 8. These mutations result in a dysfunctional protein. [14] Therefore, patients with type II HAE have normal or elevated antigenic levels of a dysfunctional mutant protein together with reduced levels of the functional protein. C1-INH deficiency allows autoactivation of C1, with consumption of C4 and C2.
In HAE with normal C1 inhibitor, the C1-INH protein is both qualitatively and functionally normal. The exact mechanism of action responsible for the link between estrogen and angioedema is unclear, thus the term “estrogen-dependent” should be avoided. The illness clearly is seen in males as well but at lower frequency. One theory suggests that estrogen plays a role in up-regulating the production of bradykinin and decreasing its degradation by angiotensin-converting enzyme (ACE).
More recently, mutations in factor XII have been identified in some, but not all patients. These factor XII mutations presumably allow for the inappropriate activation of the kinin cascade. [5]
Although urticaria and angioedema are common problems that affect nearly 20% of the population, HAE is a rare disorder. It accounts for approximately 2% of clinical angioedema cases and occurs in 1 per 50,000-150,000 population. [1] HAE leads to 15,000-30,000 emergency department visits per year in the United States.
Persons of any race can be affected by HAE, with no reported bias in different ethnic groups. Men and women are equally affected for HAE types I and II, although women tend to have more severe attacks. [1] HAE with normal C1 inhibitor levels was initially thought to occur only in women, but recent family studies have described males with HAE and normal C1 inhibitor levels. Nevertheless, HAE with normal C1 inhibitor levels is still thought to predominantly affect women.
C1-INH deficiency is present at birth in HAE, although only a few patients have been reported with perinatal angioedema. Symptoms usually become apparent in the first or second decade of life.
Approximately 40% of people with hereditary angioedema (HAE) experience their first episode before age 5 years, and 75% present before age 15 years. [18] Patients typically experience minor swelling in childhood that may go unnoticed, with increased severity around puberty. However, HAE with normal C1 inhibitor levels is found in the second decade of life or later and occurs only rarely before puberty. [5]
HAE is a lifelong affliction, although some report decreased symptoms with age. Five percent of adult HAE carriers are asymptomatic, and they are identified only after their children are found to be symptomatic.
Although rare, HAE is a disease with potentially catastrophic consequences. Laryngeal edema can result in asphyxiation. Abdominal attacks can lead to unnecessary surgery and delay in diagnosis, as well as narcotic dependence due to severe pain. Cutaneous attacks are both disfiguring and disabling, resulting in a diminished quality of life. [1]
HAE patients with an early onset of attacks have a worse prognosis than those with a late onset of attacks.
Prior to the development of effective therapy, the mortality rate was 20-30%. With appropriate use of prophylactic therapy, the prognosis for patients with HAE is now excellent. Judicious use of androgens reduces both short-term and long-term adverse effects. The advent of C1-INH concentrate and kinin pathway inhibitors will greatly enhance the care of these patients.
C1-INH is not needed for intact immune function, and patients with HAE have no increase in the incidence or severity of infections. Other biochemical pathways in which C1-INH is active, such as those for fibrinolysis and clotting, also function relatively normally without normal levels. Unlike other forms of angioedema, histamine is not involved in the pathogenesis of HAE.
Patients should be educated about possible triggering factors of their attacks. They should also be advised of the autosomal dominant inheritance pattern of HAE and that they should anticipate that 50% of their children will be affected. However, phenotypic expression of the condition may vary significantly within families.
For more information on hereditary angioedema (HAE), visit the United States Hereditary Angioedema Association. For patient education information, see the Allergy Center and Skin, Hair, and Nails Center, as well as Hives and Angioedema.
Craig T, Riedl M, Dykewicz MS, Gower RG, Baker J, Edelman FJ, et al. When is prophylaxis for hereditary angioedema necessary?. Ann Allergy Asthma Immunol. 2009 May. 102(5):366-72. [Medline].
Bankhead C. Another Drug for HAE Wins FDA Approval. MedPage Today. Jul 17 2014. [Full Text].
Riedl MA, Bernstein JA, Li H, Reshef A, Lumry W, Moldovan D, et al. Recombinant human C1-esterase inhibitor relieves symptoms of hereditary angioedema attacks: phase 3, randomized, placebo-controlled trial. Ann Allergy Asthma Immunol. 2014 Feb. 112(2):163-169.e1. [Medline].
Starr JC, Brasher GW, Rao A, Posey D. Erythema marginatum and hereditary angioedema. South Med J. 2004 Oct. 97(10):948-50. [Medline].
Bork K, Wulff K, Hardt J, Witzke G, Staubach P. Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features, trigger factors, and therapy. J Allergy Clin Immunol. 2009 Jul. 124(1):129-34. [Medline].
Weiler CR, van Dellen RG. Genetic test indications and interpretations in patients with hereditary angioedema. Mayo Clin Proc. 2006 Jul. 81(7):958-72. [Medline].
US Food and Drug Administration (FDA). FDA Approves Berinert to Treat Abdominal Attacks, Facial Swelling Associated With Hereditary Angioedema. [Full Text].
Zuraw B, Yasothan U, Kirkpatrick P. Ecallantide. Nat Rev Drug Discov. 2010 Mar. 9(3):189-90. [Medline].
Cicardi M, Banerji A, Bracho F, Malbrán A, Rosenkranz B, Riedl M, et al. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010 Aug 5. 363(6):532-41. [Medline]. [Full Text].
Lumry WR, et al. Results from FAST-3: A phase III randomized, double-blind, placebo-controlled, multicenter study of subcutaneous icatibant in patients with acute hereditary angioedema (HAE) attacks. American Academy of Allergy, Asthma, & Immunology Meeting. March 22, 2011; Abstract L2.
Zuraw BL, Busse PJ, White M, et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. 2010 Aug 5. 363(6):513-22. [Medline]. [Full Text].
Waytes AT, Rosen FS, Frank MM. Treatment of hereditary angioedema with a vapor-heated C1 inhibitor concentrate. N Engl J Med. 1996 Jun 20. 334(25):1630-4. [Medline].
Zuraw BL. Clinical practice. Hereditary angioedema. N Engl J Med. 2008 Sep 4. 359(10):1027-36. [Medline].
Cugno M, Zanichelli A, Foieni F, Caccia S, Cicardi M. C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress. Trends Mol Med. 2009 Feb. 15(2):69-78. [Medline].
Bork K. Hereditary angioedema with normal C1 inhibitor activity including hereditary angioedema with coagulation factor XII gene mutations. Immunol Allergy Clin North Am. 2006 Nov. 26(4):709-24. [Medline].
Davis AE 3rd. Mechanism of angioedema in first complement component inhibitor deficiency. Immunol Allergy Clin North Am. 2006 Nov. 26(4):633-51. [Medline].
Gompels MM, Lock RJ, Abinun M, Bethune CA, Davies G, Grattan C, et al. C1 inhibitor deficiency: consensus document. Clin Exp Immunol. 2005 Mar. 139(3):379-94. [Medline]. [Full Text].
Bork K, Meng G, Staubach P, Hardt J. Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med. 2006 Mar. 119(3):267-74. [Medline].
Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: the clinical syndrome and its management. Ann Intern Med. 1976 May. 84(5):580-93. [Medline].
Nielsen EW, Gran JT, Straume B, Mellbye OJ, Johansen HT, Mollnes TE. Hereditary angio-oedema: new clinical observations and autoimmune screening, complement and kallikrein-kinin analyses. J Intern Med. 1996 Feb. 239(2):119-30. [Medline].
Rosen FS, Alper CA, Pensky J, Klemperer MR, Donaldson VH. Genetically determined heterogeneity of the C1 esterase inhibitor in patients with hereditary angioneurotic edema. J Clin Invest. 1971 Oct. 50(10):2143-9. [Medline]. [Full Text].
Kreuz W, Martinez-Saguer I, Aygören-Pürsün E, Rusicke E, Heller C, Klingebiel T. C1-inhibitor concentrate for individual replacement therapy in patients with severe hereditary angioedema refractory to danazol prophylaxis. Transfusion. 2009 Sep. 49(9):1987-95. [Medline].
Sachse MM, Khachemoune A, Guldbakke KK, Kirschfink M. Hereditary angioedema. J Drugs Dermatol. 2006 Oct. 5(9):848-52. [Medline].
Caballero T, Farkas H, Bouillet L, Bowen T, Gompel A, Fagerberg C, et al. International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency. J Allergy Clin Immunol. 2012 Feb. 129(2):308-20. [Medline].
[Guideline] Maurer M, Mager M, Ansotegui I, Aygoren-Pursun E, Betschel S, Bork K, et al. The international WAO/EAACI guideline for the management of hereditary angioedema – the 2017 revision and update. World Allergy Organization Journal. Available at https://waojournal.biomedcentral.com/articles/10.1186/s40413-017-0180-1. 2018 Feb 27; Accessed: August 29, 2018.
Morgan BP. Hereditary angioedema–therapies old and new. N Engl J Med. 2010 Aug 5. 363(6):581-3. [Medline].
US Food and Drug Administration. Advisory Committee Briefing Document:Kalbitor (ecallantide)For Acute Attacks of Hereditary Angioedema. [Full Text].
Lumry WR, Bernstein JA, Li HH, Macginnitie AJ, Riedl M, Soteres DF, et al. Efficacy and safety of ecallantide in treatment of recurrent attacks of hereditary angioedema: Open-label continuation study. Allergy Asthma Proc. 2013 Mar. 34(2):155-61. [Medline].
Cicardi M, Levy RJ, McNeil DL, Li HH, Sheffer AL, Campion M, et al. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. 2010 Aug 5. 363(6):523-31. [Medline].
Cicardi M, Castelli R, Zingale LC, Agostoni A. Side effects of long-term prophylaxis with attenuated androgens in hereditary angioedema: comparison of treated and untreated patients. J Allergy Clin Immunol. 1997 Feb. 99(2):194-6. [Medline].
Krause K, Metz M, Zuberbier T, Maurer M, Magerl M. Successful treatment of hereditary angioedema with bradykinin B2-receptor antagonist icatibant. J Dtsch Dermatol Ges. 2010 Apr. 8(4):272-4. [Medline].
Bouillet L, Boccon-Gibod I, Ponard D, Drouet C, Cesbron JY, Dumestre-Perard C, et al. Bradykinin receptor 2 antagonist (icatibant) for hereditary angioedema type III attacks. Ann Allergy Asthma Immunol. 2009 Nov. 103(5):448. [Medline].
Cicardi M, Banerji A, Bracho F, Malbrán A, Rosenkranz B, Riedl M, et al. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010 Aug 5. 363(6):532-41. [Medline].
Bracho FA. Hereditary angioedema. Curr Opin Hematol. 2005 Nov. 12(6):493-8. [Medline].
Zuraw BL. Current and future therapy for hereditary angioedema. Clin Immunol. 2005 Jan. 114(1):10-6. [Medline].
Zuraw BL. Novel therapies for hereditary angioedema. Immunol Allergy Clin North Am. 2006 Nov. 26(4):691-708. [Medline].
American Academy of Allergy, Asthma & Immunology. Consultation and referral guidelines citing the evidence: how the allergist-immunologist can help. J Allergy Clin Immunol. 2006 Feb. 117(2 Suppl Consultation):S495-523. [Medline].
Agostoni A, Aygören-Pürsün E, Binkley KE, Blanch A, Bork K, Bouillet L, et al. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004 Sep. 114(3 Suppl):S51-131. [Medline].
Bork K, Witzke G. Long-term prophylaxis with C1-inhibitor (C1 INH) concentrate in patients with recurrent angioedema caused by hereditary and acquired C1-inhibitor deficiency. J Allergy Clin Immunol. 1989 Mar. 83(3):677-82. [Medline].
Cicardi M, Bergamaschini L, Cugno M, Hack E, Agostoni G, Agostoni A. Long-term treatment of hereditary angioedema with attenuated androgens: a survey of a 13-year experience. J Allergy Clin Immunol. 1991 Apr. 87(4):768-73. [Medline].
Gelfand JA, Sherins RJ, Alling DW, Frank MM. Treatment of hereditary angioedema with danazol. Reversal of clinical and biochemical abnormalities. N Engl J Med. 1976 Dec 23. 295(26):1444-8. [Medline].
Sheffer AL, Fearon DT, Austen KF. Clinical and biochemical effects of stanozolol therapy for hereditary angioedema. J Allergy Clin Immunol. 1981 Sep. 68(3):181-7. [Medline].
A Study of Icatibant in Patients With Acute Attacks of Hereditary Angioedema (FAST-3). [Full Text].
Bork K, Barnstedt SE, Koch P, Traupe H. Hereditary angioedema with normal C1-inhibitor activity in women. Lancet. 2000 Jul 15. 356(9225):213-7. [Medline].
EASSI – Evaluation of the Safety of Self-Administration With Icatibant. [Full Text].
Johnson K. Real-world use of icatibant improves angioedema. Medscape Medical News. November 12, 2013. [Full Text].
Leiden, The Netherlands. Biotech company Pharming Group NV (“Pharming” or “the Company”) (NYSE Euronext: PHARM) today announces that, in agreement with the European Medicines Agency (EMEA), the dossier for the European Marketing Authorisation Application (MAA) of Rhucin(R) will be submitted in September 2009. [Full Text].
Lumry WR, Li HH, Levy RJ, et al. Randomized placebo-controlled trial of the bradykinin B2 receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial. Ann Allergy Asthma Immunol. 2011 Dec. 107(6):529-37. [Medline].
Maurer M, Aberer W, Bouillet L, et al. Hereditary angioedema attacks resolve faster and are shorter after early icatibant treatment. PLoS One. 2013. 8(2):e53773. [Medline]. [Full Text].
Riedl M, Longhurst H, Fabien V, Lumry WR, Maurer M. Icatibant for the treatment of non-laryngeal hereditary angioedema attacks: comparison of outcomes from a controlled phase III trial and a real-world setting (abstract P85). Presented at: The American College of Allergy, Asthma & Immunology (ACAAI) 2013 Annual Scientific Meeting; November 9, 2013; Baltimore, Maryland.
Longhurst H, Cicardi M, Craig T, Bork K, Grattan C, Baker J, et al. Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor. N Engl J Med. 2017 Mar 23. 376 (12):1131-1140. [Medline].
Riedl M, Tachdjian R, Schranz J, Nurse C, Bernstein JA. Consistent lanadelumab treatment effect in patients with hereditary angioedema (HAE) regardless of baseline attack frequency in the phase 3 HELP study. Presented at the 2018 AAAAI/WAO Joint Congress annual meeting, March 2-5, 2018 Orlando, FL. J of Aller Clin Immunol. 2018 Feb. 141(2; suppl):AB47:[Full Text].
Michael M Frank, MD Samuel L Katz Professor of Pediatrics, Professor of Medicine and Immunology, Duke University School of Medicine, Duke University Medical Center
Michael M Frank, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Society for Pediatric Research
Disclosure: Received consulting fee from Shire for consulting; Received honoraria from Robert Michael Educationsl Institute for speaking and teaching; Received consulting fee from BioCryst for consulting.
Michael A Kaliner, MD Clinical Professor of Medicine, George Washington University School of Medicine; Medical Director, Institute for Asthma and Allergy
Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, Association of American Physicians
Disclosure: Nothing to disclose.
Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.
Warren R Heymann, MD Head, Division of Dermatology, Professor, Department of Internal Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School
Warren R Heymann, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.
Paul Krusinski, MD Director of Dermatology, Fletcher Allen Health Care; Professor, Department of Internal Medicine, University of Vermont College of Medicine
Paul Krusinski, MD is a member of the following medical societies: American Academy of Dermatology, American College of Physicians, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.
Amanda T Moon, MD Resident Physician, Department of Dermatology, University of Rochester, Strong Memorial Hospital
Amanda T Moon, MD, is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Medical Student Association/Foundation, and Society for Pediatric Dermatology
Disclosure: Nothing to disclose.
Kathleen M Rossy, MD Princeton Dermatology Associates
Disclosure: Nothing to disclose.
Robert A Schwartz, MD, MPH Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, New York Academy of Medicine, and Sigma Xi
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Michael J Wells, MD Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.
Hereditary Angioedema
Research & References of Hereditary Angioedema|A&C Accounting And Tax Services
Source
0 Comments