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Sample records for acute hereditary angioedema

  1. Ecallantide: in acute hereditary angioedema.

    Garnock-Jones, Karly P

    2010-07-30

    Ecallantide, a recombinant protein that is a selective, highly potent and reversible inhibitor of human plasma kallikrein, is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in patients aged >or=16 years. In the randomized, double-blind, placebo-controlled, multicentre, phase III trial EDEMA3, mean symptom response to treatment at 4 hours (assessed using the Treatment Outcome Score [TOS]; primary endpoint) was significantly greater with a single subcutaneous dose of ecallantide 30 mg than with placebo in patients with acute, moderate to severe attacks of HAE. In addition, the mean change from baseline in symptom severity at 4 hours (assessed using the Mean Symptom Complex Severity [MSCS] scale) was significantly greater with ecallantide than with placebo. At 4 hours in the similarly designed EDEMA4 trial, the mean change from baseline in MSCS score (primary endpoint) and mean TOS were both significantly greater in recipients of a single subcutaneous dose of ecallantide 30 mg than in placebo recipients. Subcutaneous ecallantide 30 mg was generally well tolerated in patients with acute attacks of HAE in the EDEMA3 and EDEMA4 trials. Adverse events were mostly of mild to moderate severity, and no event that was more common in ecallantide than placebo recipients occurred in >10% of patients. PMID:20614949

  2. Hereditary Angioedema Presenting as Recurrent Acute Pancreatitis.

    Berger, Tal D; Garty, Ben-Zion

    2016-02-01

    Hereditary angioedema (HAE) may manifest with swelling of the face, extremities, and upper airways. Gastrointestinal symptoms are also common and may include abdominal pain, vomiting, and diarrhea. However, pancreatic involvement is rare and has been reported only in a few adults with previously diagnosed HAE. We describe a 6-year-old boy who presented with recurrent severe abdominal pain accompanied by an elevation in pancreatic enzyme levels, without subcutaneous or cutaneous angioedema. His symptoms had begun 18 months earlier, and he was hospitalized several times before the present admission with a diagnosis of acute pancreatitis. More comprehensive analysis yielded low levels of C2, C4, CH50, and C1 esterase inhibitor, establishing the diagnosis of HAE. One year after diagnosis, swelling of the extremities appeared for the first time. This is the first report of a child in whom pancreatic disease was the presenting symptom of HAE. HAE should be included in the differential diagnosis of recurrent pancreatitis in children. PMID:26812927

  3. Hereditary Angioedema

    Abdel-Karim, Omar; Dizdarevic, Adis; Bygum, Anette

    2014-01-01

    Hereditary angioedema is an inherited disease that causes periodic swelling attacks, which can be life threatening and have a major effect on a patient's life. Studies have shown that home therapy for angioedema reduces disease severity, leads to faster relief of symptoms, and improves quality of...

  4. An overview of novel therapies for acute hereditary angioedema.

    Firszt, Rafael; Frank, Michael M

    2010-12-01

    Hereditary angioedema is an episodic swelling disorder with autosomal dominant inheritance. Attacks are characterized by nonpitting edema of external or mucosal body surfaces. Patients often present with swelling of the extremities, abdominal pain, and swelling of the mouth and throat, which can at times lead to asphyxiation. The disease is caused by a mutation in the gene encoding the complement C1-inhibitor protein, which leads to unregulated production of bradykinin. Long-term therapy has depended on the use of attenuated androgens or plasmin inhibitors but in the US there was, until recently, no specific therapy for acute attacks. As well, many patients with hereditary angioedema in the US were either not adequately controlled on previously available therapies or required doses of medications that exposed them to the risk of serious adverse effects. Five companies have completed or are currently conducting phase III clinical trials in the development of specific therapies to terminate acute attacks or to be used as prophylaxis. These products are based on either replacement therapy with purified plasma-derived or recombinant C1-inhibitor, or inhibition of the kinin-generating pathways with a recombinant plasma kallikrein inhibitor or bradykinin type 2 receptor antagonist. Published studies thus far suggest that all of these products are likely to be effective. These new therapies will likely lead to a totally new approach in treating hereditary angioedema. PMID:20866113

  5. Management of acute attacks of hereditary angioedema: role of ecallantide

    Duffey H

    2015-04-01

    Full Text Available Hannah Duffey,1 Rafael Firszt1,2 1Department of Pediatrics, 2Division of Allergy, Immunology and Rheumatology, University of Utah, Salt Lake City, UT, USA Abstract: Hereditary angioedema (HAE is characterized as an episodic swelling disorder with autosomal dominant inheritance. Clinical features include nonpitting edema of external or mucosal body surfaces, and patients often present with swelling of the extremities, abdominal pain, and swelling of the mouth and throat, which can lead to asphyxiation. Patients with HAE classically have no associated urticaria, which is often referred to as nonhistaminergic angioedema. Treatment for HAE involves long-term prophylaxis, short-term prophylaxis, and management of acute attacks. Up until the past few years, acute HAE episodes were predominately treated with supportive measures. Three classes of medications have recently been approved by the US Food and Drug Administration (FDA for the management of acute HAE attacks. Ecallantide, a recombinant protein that acts as a reversible inhibitor of kallikrein, is currently indicated for acute attacks of HAE in those aged 12 years. In two randomized, double-blind, placebo-controlled, multicenter trials, EDEMA3 and EDEMA4, patients treated with 30 mg of ecallantide demonstrated statistically significant improvement in symptoms compared to those on placebo. In addition to its use as treatment for HAE, ecallantide has been used off label in the management of nonhistaminergic angioedema, not due to HAE. Ecallantide has shown promise in the treatment of these other forms; however, data are limited to mainly case reports at this time. Ecallantide is generally a safe and well-tolerated medication; however, based on reports of anaphylaxis, ecallantide does contain a black box warning. Due to the risk of anaphylaxis, ecallantide cannot be self-administered and must be given by a health care professional. Overall, ecallantide is a safe and effective medication for the

  6. [Hereditary angioedema].

    Bouchard, Laura J; Hyry, Heli; Meri, Seppo

    2012-01-01

    Hereditary angioedema (HAE) is a rare autosomal dominant disease characterized by episodic swelling of the face, extremities, larynx, gastrointestinal tract or genitals. Three different subtypes have been identified so far. Type I and II HAE are caused by mutations in the C1 inhibitor gene leading to decreased or dysfunctional C1 inhibitor, respectively. Type III is caused by a mutation in the coagulation factor XII. In addition, acquired forms or forms with no known etiology exist. Increased bradykinin production leading to increased vessel permeability is common to all HAE types. Treatment of HAE has evolved dramatically during the last years as self-administration of C1 inhibitor concentrate and bradykinin-2 receptor antagonist icatibant have become available. PMID:23393928

  7. Management of acute attacks of hereditary angioedema: role of ecallantide

    Duffey, Hannah; Firszt, Rafael

    2015-01-01

    Hereditary angioedema (HAE) is characterized as an episodic swelling disorder with autosomal dominant inheritance. Clinical features include nonpitting edema of external or mucosal body surfaces, and patients often present with swelling of the extremities, abdominal pain, and swelling of the mouth and throat, which can lead to asphyxiation. Patients with HAE classically have no associated urticaria, which is often referred to as nonhistaminergic angioedema. Treatment for HAE involves long-term prophylaxis, short-term prophylaxis, and management of acute attacks. Up until the past few years, acute HAE episodes were predominately treated with supportive measures. Three classes of medications have recently been approved by the US Food and Drug Administration (FDA) for the management of acute HAE attacks. Ecallantide, a recombinant protein that acts as a reversible inhibitor of kallikrein, is currently indicated for acute attacks of HAE in those aged ≥12 years. In two randomized, double-blind, placebo-controlled, multicenter trials, EDEMA3 and EDEMA4, patients treated with 30 mg of ecallantide demonstrated statistically significant improvement in symptoms compared to those on placebo. In addition to its use as treatment for HAE, ecallantide has been used off label in the management of nonhistaminergic angioedema, not due to HAE. Ecallantide has shown promise in the treatment of these other forms; however, data are limited to mainly case reports at this time. Ecallantide is generally a safe and well-tolerated medication; however, based on reports of anaphylaxis, ecallantide does contain a black box warning. Due to the risk of anaphylaxis, ecallantide cannot be self-administered and must be given by a health care professional. Overall, ecallantide is a safe and effective medication for the treatment of acute attacks of HAE. PMID:25931832

  8. Idiopathic Thrombocytopenic Purpura Misdiagnosed as Hereditary Angioedema

    Andersen, Michelle Fog; Bygum, Anette

    2015-01-01

    Hereditary angioedema is a rare, but potentially life-threatening genetic disorder that results from an autosomal dominant trait. It is characterized by acute, recurrent attacks of severe local edema, most commonly affecting the skin and mucosa. Swelling in hereditary angioedema patients does however not always have to be caused by angioedema but can relate to other concomitant disorders. In this report we are focusing on misdiagnosis in a patient with known hereditary angioedema, whose bleeding episode caused by idiopathic thrombocytopenic purpura was mistaken for an acute attack of hereditary angioedema. The case illustrates how clinicians can have difficulties in handling patients with rare diseases, especially in the emergency care setting. PMID:26819784

  9. Idiopathic Thrombocytopenic Purpura Misdiagnosed as Hereditary Angioedema

    Andersen, Michelle Fog; Bygum, Anette

    2015-01-01

    Hereditary angioedema is a rare, but potentially life-threatening genetic disorder that results from an autosomal dominant trait. It is characterized by acute, recurrent attacks of severe local edema, most commonly affecting the skin and mucosa. Swelling in hereditary angioedema patients does...... however not always have to be caused by angioedema but can relate to other concomitant disorders. In this report we are focusing on misdiagnosis in a patient with known hereditary angioedema, whose bleeding episode caused by idiopathic thrombocytopenic purpura was mistaken for an acute attack of...... hereditary angioedema. The case illustrates how clinicians can have difficulties in handling patients with rare diseases, especially in the emergency care setting....

  10. [Diagnosis of hereditary angioedema].

    Bouillet, Laurence

    2015-01-01

    Hereditary angioedema is a rare disease, potentially life-threatening. It requires a specific treatment. Angioedema without wheals associated with abdominal attacks are very specific of this disease. Antigenemy and functional C1Inhibitor assays are necessary for the diagnosis. The hereditary angioedema with normal C1Inh (type III) is a diagnostic challenge. Bradykinin, secondary to kallikrein-kinin system activation is the key mediator of hereditary angioedema. Female are more symptomatic. Attacks can be induced by menstruations, pregnancies or contraceptive pills. PMID:25511656

  11. Hereditary angioedema type 2 presented as an orbital complication of acute rhinosinusitis.

    Somuk, Battal Tahsin; Göktas, Göksel; Özer, Samet; Sapmaz, Emrah; Bas, Yalcın

    2016-03-01

    Hereditary angioedema is an autosomal dominant and life-threatening disorder characterized by recurrent episodes of non-pitting edema affecting the skin, respiratory system and digestive tracts and caused by a congenital deficiency or function defect of the C1 esterase inhibitor. Preseptal cellulitis is defined as an infection of the tissues of the anterior orbital septum. It is generally caused by complications from an upper respiratory tract infection, dacryocystitis, dermal infection, and, rarely, sinusitis. The disease presents with orbital pain, edema on the eyelids, erythema, and fever. In this case, a child with hereditary angioedema type 2 who presented as mimicking a complication of acute sinusitis is discussed. PMID:26857308

  12. Hereditary Angioedema in Childhood

    Kjaer, Line; Bygum, Anette

    2012-01-01

    Hereditary angioedema (HAE) is a rare inherited disease that is often difficult to diagnose. We report a case of a 9-year-old boy with a spontaneous mutation causing HAE, diagnosed after a life-threatening episode of angioedema of the head and upper respiratory tract after a 5-year history of...

  13. Management of acute attacks of hereditary angioedema: potential role of icatibant

    Hilary J Longhurst

    2010-09-01

    Full Text Available Hilary J LonghurstDepartment of Immunology, Barts and The London NHS Trust, London, UKAbstract: Icatibant (Firazyr® is a novel subcutaneous treatment recently licensed in the European Union for acute hereditary angioedema. Hereditary angioedema, resulting from inherited partial C1 inhibitor deficiency, is a disabling condition characterized by intermittent episodes of bradykinin-mediated angioedema. Icatibant blocks bradykinin B2 receptors, attenutating the episode. Randomized double-blind, placebo-controlled trials of icatibant, showed significant superiority over oral tranexamic acid in 74 European patients and a trend to improvement in a similar US trial comparing icatibant with placebo in 55 patients. Outcomes for several endpoints did not reach significance in the US trial, perhaps because of low participant numbers and confounding factors: a further trial is planned. Open label studies have shown benefit in multiple treatments for attacks at all sites. Approximately 10% of patients require a second dose for re-emergent symptoms, usually 10 to 27 hours after the initial treatment. Its subcutaneous route of administration, good tolerability and novel mode of action make icatibant a promising addition to the limited repertoire of treatments for hereditary angioedema.Keywords: hereditary angioedema, bradykinin, icatibant, C1 inhibitor deficiency

  14. Icatibant for hereditary angioedema.

    Gras, Jordi

    2009-12-01

    Hereditary angioedema (HAE) is an autosomal dominant, potentially life-threatening disease, characterized by recurrent self-limiting bouts of edema mainly involving the extremities, genitalia, face, intestines and airways. The prevalence of HAE in the general population has been estimated to be in the range of 1:10,000 to 1:150,000. Currently, acute attacks of HAE are treated mainly symptomatically, with poor outcomes. Recently, it has been demonstrated that bradykinin (BK) is responsible for most of the symptoms of HAE. Icatibant (Firazyr, HOE 140, JE049) is a potent, specific and selective B2 BK receptor antagonist that has recently been approved by the EMEA for the treatment of HAE. In phase III clinical trials, 30 mg of subcutaneous icatibant demonstrated rapid and stable relief from symptoms in cutaneous, abdominal or laryngeal HAE attacks. Local site reactions after subcutaneous injection of icatibant were observed, however, these reactions were mild to moderate in severity and resolved spontaneously and quickly. Icatibant is a new, safe and effective treatment for acute attacks of HAE. PMID:20135020

  15. Prospective, double-blind, placebo-controlled trials of ecallantide for acute attacks of hereditary angioedema.

    Stolz, Leslie E; Sheffer, Albert L

    2012-01-01

    Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable, episodic, incapacitating attacks of well-demarcated angioedema in the absence of urticaria and pruritus. HAE is due to deficient or dysfunctional C1-esterase inhibitor activity, which results in unopposed activation of plasma kallikrein, resulting in increased levels of bradykinin. Ecallantide is a potent and specific plasma kallikrein inhibitor approved for the treatment of acute attacks of HAE affecting any anatomic site. In Phase III clinical trials, subcutaneously administered ecallantide demonstrated significant, rapid and durable symptom relief. Ecallantide was effective for all attack types, including potentially life-threatening laryngeal attacks. The main safety concern is potentially serious hypersensitivity reactions, including anaphylaxis. Ecallantide represents an important treatment option for the management of acute attacks of HAE. PMID:22149337

  16. Hereditary angioedema: Not an allergy

    Sanjay Bhivgade

    2012-01-01

    Full Text Available Hereditary angioedema is a genetic disorder due to a deficiency or malfunction of C1 esterase inhibitor. We herein describe a case of 25-year-old male who presented with swelling over face since one day. There was history of similar episodes since two years with gradual subsidence of swelling without any treatment. Investigations revealed grossly reduced complement C4 and C1 esterase inhibitor level. Patient was diagnosed to have hereditary angioedema type 1 and started on stanozolol 2 mg three times a day with no recurrence in one year of follow-up. Hereditary angioedema resembles angioedema of an allergic reaction. However, the cause is different.

  17. Hereditary angioedema in women

    Bouillet Laurence

    2010-07-01

    Full Text Available Abstract Women with hereditary angioedema (HAE are more likely to be symptomatic that men. Hormonal factors (puberty, contraception, pregnancy,.... play a significant role in the precipitation or worsening of the condition in women. So, combined contraceptive pills are not indicated and progestogen pill must be preferred. During pregnancy, attack rate can increase (38-48% of women. C1Inhibitor concentrate and tranexamic acid can be used during pregnancy. Attenuated androgens for long term prophylaxis are effective but side effects appear more often in female patients. These side effects are dose dependant and can be attenuated by titrating the dose down the lowest effective level.

  18. Fresh Frozen Plasma for the Treatment of Hereditary Angioedema Acute Attacks

    Rui Tang; Shi Chen; Hong-yu Zhang

    2012-01-01

    Objective To determine the safety and efficacy of fresh frozen plasma (FFP) infusion for the treatment of hereditary angioedema (HAE).Methods The medical records of patients with HAE admitted to Peking Union Medical College Hospital who had received FFP infusion during 2004 and 2010 were reviewed and PubMed database from 1966 to the present were searched using the following key words:hereditary angioedema and fresh frozen plasma.The patient's age,sex,body location of HAE attacks,the dose of FFP infusion,time of beginning to improvement,time to complete remission,complication,C1 inhibitor activity,and outcome were analyzed.Results A total of 13 enrolled patients (7 male and 6 female) received 16 times of FFP infusion,including 2 patients undergoing FFP infusion in Peking Union Medical College Hospital and 11 patients reported in the literature.The mean dosage of FFP infusion was 586±337 mL.Two cases suffered from worsening abdominal pain and one case experienced skin rash.Only 1 patient had no improvement in symptom owing to transfusion related reaction.There was a defimite improvement in symptom 49± 19 minutes after beginning FFP infusion.The remission time decreased from 61.7±27.0 hours to 3.3 (2.0,12.0) hours after FFP infusion.FFP infusion was effective for both type Ⅰ and type Ⅱ HAE.Conclusion FFP seems to be safe and effective for acute attacks of HAE.

  19. Safety of C1-Esterase Inhibitor in Acute and Prophylactic Therapy of Hereditary Angioedema

    Busse, Paula; Bygum, Anette; Edelman, Jonathan; Lumry, William; Machnig, Thomas; Martinez-Saguer, Inmaculada; Rojavin, Mikhail

    2014-01-01

    BACKGROUND: The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate, Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a substantial literature base that demonstrates safety and efficacy. Thromboembolic events have rarely been reported with C1-INH products...

  20. Ecallantide: a plasma kallikrein inhibitor for the treatment of acute attacks of hereditary angioedema.

    Stolz, L E; Horn, P T

    2010-08-01

    Hereditary angioedema (HAE) is a debilitating, potentially fatal disease characterized by variable and unpredictable acute attacks of swelling affecting the subcutaneous tissue and mucosa. It is an autosomal dominant disorder resulting from a genetic deficiency of functional C1-esterase inhibitor. Available treatments include long-term prophylaxis, short-term prophylaxis and treatment of acute attacks. Ecallantide is a novel, specific and potent inhibitor of plasma kallikrein that was recently approved in the United States for the treatment of acute attacks of HAE in patients aged 16 years and older. In two phase III clinical trials, the subcutaneous administration of 30 mg ecallantide resulted in significantly greater symptom improvement than placebo for acute attacks of HAE. Ecallantide was generally well tolerated throughout the clinical development program. The main safety concern following ecallantide treatment is hypersensitivity reactions, including anaphylaxis. A Risk Evaluation and Management Strategy (REMS) has been implemented to minimize this risk and a long-term observational safety study is currently under way to collect more information about hypersensitivity and immunogenicity. Ecallantide represents a novel treatment option for patients with HAE. PMID:20830315

  1. Angioedema hereditario en pediatría Hereditary pediatric angioedema

    A. Calvo Gómez-Rodulfo

    2009-01-01

    Full Text Available

    Introducción: El angioedema hereditario es una patología de origen genético causada por la alteración del gen que codifica la proteína inhibidora de la C1 esterasa activada (C1-INH. La prevalencia de esta entidad es baja, lo que dificulta su diagnóstico y manejo adecuado.
    Caso clínico: Se presenta el caso de una paciente con episodios repetidos de edema subcutáneo localizado en las extremidades desde los tres años de vida, añadiendo disfagia y disfonía a partir de la pubertad. Su madre y un hermano presentaban sintomatología similar. En los tres casos se demostró deficiencia de C1-INH, siendo diagnosticados de angioedema hereditario.
    Conclusiones: El angioedema hereditario es una entidad poco frecuente y potencialmente grave. Aunque la sintomatología puede ser similar a cuadros alérgicos y anafilácticos, el manejo es muy diferente, siendo la administración intravenosa de C1-INH de elección en el tratamiento del episodio agudo grave. Debe considerarse también la necesidad de tratamiento profiláctico a largo plazo ante el antecedente de episodio de angioedema grave o cuando los episodios se repitan frecuentemente. En este artículo se revisan los distintos aspectos diagnósticos y terapéuticos del angioedema hereditario.

    Introduction: The hereditary angioedema is a rare genetical disease caused by deficiency of C1 esterase inhibitor (C1-INH. The diagnosis is difficult because the low prevalence f it.
    Clinical report: We show a female with recurrent episodes of edema in extremities since 3 years old, with dysphagia and voice change since puberty. Her mother and brother had similar manifestations. All they were diagnosed of hereditary angioedema with C1-INH deficiency.
    Conclusions: The hereditary angioedema is a rare and potential severe disease. Its manifestations may be similar to the allergy or anaphylaxis, but its treatment is different. Emergency therapy of acute oedematous attacks with C1

  2. Treatment response after repeated administration of C1 esterase inhibitor for successive acute hereditary angioedema attacks.

    Craig, Timothy J; Bewtra, Againdra K; Hurewitz, David; Levy, Robyn; Janss, Gerti; Jacobson, Kraig W; Packer, Flint; Bernstein, Jonathan A; Rojavin, Mikhail A; Machnig, Thomas; Keinecke, Heinz-Otto; Wasserman, Richard L

    2012-01-01

    Placebo-controlled studies established the efficacy of replacement therapy with C1 esterase inhibitor (C1-INH) concentrate for treating single acute hereditary angioedema (HAE) attacks, but only limited data from prospective studies are available on repeated treatment of successive HAE attacks. This study evaluates the association between repeated treatments with 20 U/kg of C1-INH concentrate (Berinert; CSL Behring, Marburg, Germany) for HAE attacks at any body location and treatment response. In a post hoc analysis of an open-label extension study (International Multicenter Prospective Angioedema C1-INH Trial [I.M.P.A.C.T.2]), the association between repeated treatment with C1-INH and times to onset of symptom relief and complete resolution of HAE symptoms was assessed in patients who were treated for at least 15 attacks by linear regression on the ordinal attack number. Eighteen patients received C1-INH concentrate for at least 15 HAE attacks over a mean duration of 34 months. Demographic and baseline characteristics of these patients were similar to those of all patients in the study. The distribution of body locations and the intensity of HAE attacks were similar for each of the first 15 attacks and subsequent attacks. The extent of previous use of C1-INH concentrate had no effect on the time to onset of symptom relief, the time to complete resolution of HAE symptoms, or the time between attacks treated with C1-INH concentrate; the median of individual linear regression coefficients was not statistically significantly different from 0. Treatment with 20 U/kg of C1-INH concentrate provided consistent treatment response in patients treated for multiple successive HAE attacks at any body location. (Clinicaltrials.gov identifier: NCT00292981). PMID:22856636

  3. Socioeconomic burden of hereditary angioedema

    Aygören-Pürsün, Emel; Bygum, Anette; Beusterien, Kathleen;

    2014-01-01

    BACKGROUND: Hereditary angioedema (HAE) due to C1 inhibitor deficiency is a rare but serious and potentially life-threatening disease marked by spontaneous, recurrent attacks of swelling. The study objective was to characterize direct and indirect resource utilization associated with HAE from the...

  4. Safety and efficacy of icatibant self-administration for acute hereditary angioedema.

    Boccon-Gibod, I; Bouillet, L

    2012-06-01

    We evaluated the efficacy and safety of icatibant self-administration in 15 patients with hereditary angioedema (HAE) types I or III, for 55 acute attacks (mostly severe or very severe). Icatibant self-administration was generally effective: first symptom improvement occurred in 5 min-2 h (HAE type I; n = 17) and 8 min-1 h (HAE type III; n = 9) for abdominal attacks and 5-30 min (HAE type I; n = 4) and 10 min-12 h (HAE type III; n = 6) for laryngeal attacks. Complete symptom resolution occurred in 15 min-19 h (HAE type I; n = 8) and 15 min-48 h (HAE type III; n = 9) for abdominal attacks and 5-48 h (HAE type I; n = 3) and 8-48 h (HAE type III; n = 5) for laryngeal attacks. No patient required emergency hospitalization. The only adverse events were mild, spontaneously resolving injection site reactions. Patients reported that carrying icatibant with them gave them greater confidence in managing their condition. PMID:22519593

  5. Clinical efficacy of icatibant in the treatment of acute hereditary angioedema during the FAST-3 trial.

    Baş, Murat

    2012-11-01

    Bradykinin is the key mediator of symptoms of hereditary angioedema (HAE), a rare genetic disorder characterized by recurrent episodes of edema of the skin, mucosa and muscle. Icatibant, a bradykinin B(2) receptor antagonist, is an effective and generally well-tolerated treatment option for acute attacks of type I and II HAE. A Phase III randomized, double-blind, placebo-controlled study, FAST-3 (NCT00912093), was designed to further evaluate the efficacy and safety of icatibant in patients presenting with moderate to very severe cutaneous and/or abdominal or mild-to-moderate laryngeal symptoms. Severe laryngeal attacks were treated with open-label icatibant. The controlled phase of FAST-3, completed in October 2010 with results published in December 2011, demonstrated that compared with placebo, icatibant evoked clinically meaningful and statistically significant efficacy across multiple end points in the treatment of type I and II HAE attacks. In addition, icatibant was generally well tolerated and no drug-related serious adverse events were experienced. PMID:23167682

  6. Brazilian guidelines for the diagnosis and treatment of hereditary angioedema

    Pedro Giavina-Bianchi

    2011-01-01

    Full Text Available Hereditary angioedema is an autosomal dominant disease characterized by edema attacks with multiple organ involvement. It is caused by a quantitative or functional deficiency of the C1 inhibitor, which is a member of the serine protease inhibitor family. Hereditary angioedema is unknown to many health professionals and is therefore an underdiagnosed disease. The causes of death from hereditary angioedema include laryngeal edema with asphyxia. The estimated mortality rate in patients in whom the disease goes undetected and who are therefore incorrectly treated is 25-40%. In addition to edema of the glottis, hereditary angioedema often results in edema of the gastrointestinal tract, which can be incapacitating. Patients with hereditary angioedema may undergo unnecessary surgical interventions because the digestive tract can be the primary or only organ system involved, thus mimicking acute surgical abdomen. It is estimated that patients with hereditary angioedema experience some degree of disability 20-100 days per year. The Experts in Clinical Immunology and Allergy of the "Associação Brasileira de Alergia e Imunopatologia -ASBAI" developed these guidelines for the diagnosis, therapy, and management of hereditary angioedema.

  7. Disease expression in women with hereditary angioedema

    Bouillet, Laurence; Longhurst, Hilary; Boccon-Gibod, Isabelle;

    2008-01-01

    OBJECTIVE: Fluctuations in sex hormones can trigger angioedema attacks in women with hereditary angioedema. Combined oral contraceptive therapies, as well as pregnancy, can induce severe attacks. The course of angioedema may be very variable in different women. STUDY DESIGN: Within the PREHAEAT...... project launched by the European Union, data on 150 postpubertal women with hereditary angioedema were collected in 8 countries, using a patient-based questionnaire. RESULTS: Puberty worsened the disease for 62%. Combined oral contraceptives worsened the disease for 79%, whereas progestogen-only pills...

  8. A Rare Cause of Abdominal Pain in Children: Hereditary Angioedema

    Deniz Özçeker

    2015-03-01

    Full Text Available Hereditary angioedema (HA is a rare, autosomal-dominant genetic disorder presenting with recurrent attacks of angioedema. The most commonly involved organs include the extremites, face, neck, upper respiratory tract, genital region and the gastrointestinal tract. Edema of the intestinal mucosa can cause temporary obstruction and severe abdominal pain that can be confused with acute abdomen. Pediatricians and emergency physicians should keep in mind this rare disease in the differential diagnosis of severe abdominal pain.

  9. Benefits and risks of danazol in hereditary angioedema

    Bork, Konrad; Bygum, Anette; Hardt, Jochen

    2008-01-01

    BACKGROUND: Hereditary angioedema (HAE) due to C1 inhibitor deficiency is clinically characterized by relapsing skin swellings, abdominal pain attacks, and life-threatening upper airway obstruction. Treatment with androgens prevents attacks for those with this condition. OBJECTIVE: To examine the...... other patients, hereditary angioedema ran a mild course. The frequency of acute attacks during danazol treatment was reduced to 16.2%, and the attacks were considerably milder than before treatment. Laryngeal edema was reduced to 4.8%. Adverse effects (weight gain, virilization, menstrual irregularities...

  10. An evidence-based review of the potential role of icatibant in the treatment of acute attacks in hereditary angioedema type I and II

    Floccard B

    2012-09-01

    Full Text Available Bernard Floccard,1 Etienne Hautin,1 Laurence Bouillet,2 Brigitte Coppere,3 Bernard Allaouchiche11Département d'Anesthésie Réanimation, Centre de Référence des Angiœdèmes à Bradykinine, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, 2Clinique Universitaire de Médecine Interne, Centre National de Référence des Angiœdèmes à Bradykinine, CHU de Grenoble, Grenoble, 3Service de Médecine Interne, Centre de Référence des Angiœdèmes à Bradykinine, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, FranceIntroduction: Icatibant, a first-in-class B2 bradykinin receptor antagonist, appears to have a favorable efficacy and safety profile for the treatment of acute attacks of hereditary angioedema in adults.Aims: To update the evidence and provide an overview of the available data on icatibant.Evidence review: Peer reviewed articles published and listed in Medline Search and published updated guidelines for the treatment of acute attacks in hereditary angioedema type I and II in adults were reviewed. The validity and quality of evidence were evaluated.Place in therapy: Clinical evidence for the treatment of acute hereditary angioedema attacks with icatibant is strong. Approximately 10% of the patients require a second dose. No serious adverse reactions have been reported. The only significant side effects consistently registered by 90% of patients are transient local pain, swelling, and erythema at the local injection site.Conclusion: Subcutaneously administered 30 mg icatibant has been shown to be a safe and efficacious treatment in clinical trials. It is the only specific treatment authorized for self-administration by the subcutaneous route offering increased patient independence.Keywords: icatibant, hereditary angioedema, self-administration, acute attacks

  11. Epidemiology of Non-hereditary Angioedema

    Madsen, Flemming; Attermann, Jorn; Linneberg, Allan

    2012-01-01

    The prevalence of non-hereditary angioedema was investigated in a general population sample (n = 7,931) and in a sample of Danish patients (n = 7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate...... abdominal area, 17% had diarrhoea, 11% had vomiting and 6% fainted during attacks. Non-hereditary angioedema has high lifetime prevalence and becomes chronic in approximately 50% of affected patients. Symptoms in the larynx and throat, as well as non-specific symptoms, such as dizziness and abdominal pain......) reported a lifetime prevalence of 7.4% for angioedema. In both groups symptoms were most frequent in the lips, head, neck, eyes and tongue. In the C1 INH test normal group angioedema was still active at the time of the study in 53% of the patients, and 36% reported symptoms in the throat, 23% in the...

  12. Coexistence of hereditary angioedema and Turner's syndrome.

    Fletcher, A; Weetman, A P

    1998-01-01

    A 34-year-old woman presented to the out-patient clinic with angioedema and type II hereditary angioedema was confirmed immunologically. She also volunteered she had never had a menstrual period and physical examination identified several features of Turner's syndrome. A mosaic karyotype with XY and XO was found on chromosomal analysis and gonadectomy was performed in view of the high risk of gonadoblastoma. After commencing oestrogen at physiological replacement doses, the patient experience...

  13. New treatments addressing the pathophysiology of hereditary angioedema

    Davis Alvin E

    2008-04-01

    Full Text Available Abstract Hereditary angioedema is a serious medical condition caused by a deficiency of C1-inhibitor. The condition is the result of a defect in the gene controlling the synthesis of C1-inhibitor, which regulates the activity of a number of plasma cascade systems. Although the prevalence of hereditary angioedema is low – between 1:10,000 to 1:50,000 – the condition can result in considerable pain, debilitation, reduced quality of life, and even death in those afflicted. Hereditary angioedema presents clinically as cutaneous swelling of the extremities, face, genitals, and trunk, or painful swelling of the gastrointestinal mucosa. Angioedema of the upper airways is extremely serious and has resulted in death by asphyxiation. Subnormal levels of C1-inhibitor are associated with the inappropriate activation of a number of pathways – including, in particular, the complement and contact systems, and to some extent, the fibrinolysis and coagulation systems. Current findings indicate bradykinin, a product of contact system activation, as the primary mediator of angioedema in patients with C1-inhibitor deficiency. However, other systems may play a role in bradykinin's rapid and excessive generation by depleting available levels of C1-inhibitor. There are currently no effective therapies in the United States to treat acute attacks of hereditary angioedema, and currently available agents used to treat hereditary angioedema prophylactically are suboptimal. Five new agents are, however, in Phase III development. Three of these agents replace C1-inhibitor, directly addressing the underlying cause of hereditary angioedema and re-establishing regulatory control of all pathways and proteases involved in its pathogenesis. These agents include a nano-filtered C1-inhibitor replacement therapy, a pasteurized C1-inhibitor, and a recombinant C1-inhibitor isolated from the milk of transgenic rabbits. All C1-inhibitors are being investigated for acute angioedema

  14. New treatments addressing the pathophysiology of hereditary angioedema.

    Davis, Alvin E

    2008-01-01

    Hereditary angioedema is a serious medical condition caused by a deficiency of C1-inhibitor. The condition is the result of a defect in the gene controlling the synthesis of C1-inhibitor, which regulates the activity of a number of plasma cascade systems. Although the prevalence of hereditary angioedema is low - between 1:10,000 to 1:50,000 - the condition can result in considerable pain, debilitation, reduced quality of life, and even death in those afflicted. Hereditary angioedema presents clinically as cutaneous swelling of the extremities, face, genitals, and trunk, or painful swelling of the gastrointestinal mucosa. Angioedema of the upper airways is extremely serious and has resulted in death by asphyxiation.Subnormal levels of C1-inhibitor are associated with the inappropriate activation of a number of pathways - including, in particular, the complement and contact systems, and to some extent, the fibrinolysis and coagulation systems.Current findings indicate bradykinin, a product of contact system activation, as the primary mediator of angioedema in patients with C1-inhibitor deficiency. However, other systems may play a role in bradykinin's rapid and excessive generation by depleting available levels of C1-inhibitor.There are currently no effective therapies in the United States to treat acute attacks of hereditary angioedema, and currently available agents used to treat hereditary angioedema prophylactically are suboptimal. Five new agents are, however, in Phase III development. Three of these agents replace C1-inhibitor, directly addressing the underlying cause of hereditary angioedema and re-establishing regulatory control of all pathways and proteases involved in its pathogenesis. These agents include a nano-filtered C1-inhibitor replacement therapy, a pasteurized C1-inhibitor, and a recombinant C1-inhibitor isolated from the milk of transgenic rabbits. All C1-inhibitors are being investigated for acute angioedema attacks; the nano-filtered C1

  15. Genetics Home Reference: hereditary angioedema

    ... Cicardi M. C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress. Trends Mol Med. 2009 Feb; ... with a qualified healthcare professional . About Genetics Home Reference Site Map Contact Us Selection Criteria for Links ...

  16. Management of hereditary angioedema: 2010 Canadian approach

    Bowen Tom

    2010-07-01

    Full Text Available Abstract C1-inhibitor (C1-INH deficiency is a rare blood disorder resulting in angioedema attacks that are debilitating and may be life-threatening. Prophylaxis and therapy of events has changed since our first Canadian Consensus Conference on the diagnosis, therapy and management of HAE. We have formed the Canadian Hereditary Angioedema Network (CHAEN/Réseau Canadien d'Angioédème Héréditaire (RCAH - http://www.haecanada.com to advance care of patients with this disorder in Canada. We here present a review of management of HAE in Canada.

  17. Epidemiology of Non-hereditary Angioedema

    Madsen, Flemming; Attermann, Jørn; Linneberg, Allan

    The prevalence of non-hereditary angioedema was investigated in a general population sample (n¿=¿7,931) and in a sample of Danish patients (n¿=¿7,433) tested for deficiency of functional complement C1 esterase inhibitor protein (functional C1 INH). The general population sample (44% response rate...... abdominal area, 17% had diarrhoea, 11% had vomiting and 6% fainted during attacks. Non-hereditary angioedema has high lifetime prevalence and becomes chronic in approximately 50% of affected patients. Symptoms in the larynx and throat, as well as non-specific symptoms, such as dizziness and abdominal pain......) reported a lifetime prevalence of 7.4% for angioedema. In both groups symptoms were most frequent in the lips, head, neck, eyes and tongue. In the C1 INH test normal group angioedema was still active at the time of the study in 53% of the patients, and 36% reported symptoms in the throat, 23% in the...

  18. Hereditary Angioedema - Consequences of a New Treatment Paradigm in Denmark

    Bygum, Anette

    2014-01-01

    Experiences from a Danish patient cohort with hereditary angioedema are reported with focus on home therapy and burden of illness. Eighty patients have been prospectively followed over 11 years, having experienced a total of 7,809 attacks over 469 patient years. More than half of the patients...... stopped long-term prophylaxis with danazol or tranexamic acid and changed treatment regimen to on-demand treatment with C1 inhibitor concentrate or icatibant. At least 10% of the attacks remained un-treated. More than half of the patients felt that hereditary angioedema had a significant psychological...... therapy has profoundly improved the lives of hereditary angioedema patients....

  19. Angioedema.

    Kaplan, Allen P

    2008-06-01

    Angioedema can be caused by either mast cell degranulation or activation of the kallikrein-kinin cascade. In the former case, angioedema can be caused by allergic reactions caused by immunoglobulin E (IgE)-mediated hypersensitivity to foods or drugs that can also result in acute urticaria or a more generalized anaphylactic reaction. Nonsteroidal anti-inflammatory drugs (cyclooxygenase 1 inhibitors, in particular) may cause angioedema with or without urticaria, and leukotrienes may have a particular role as a mediator of the swelling. Reactions to contrast agents resemble allergy with basophil and mast cell degranulation in the absence of specific IgE antibody and can be generalized, that is, anaphylactoid. Angioedema accompanies chronic urticaria in 40% of patients, and approximately half have an autoimmune mechanism in which there is IgG antibody directed to the subunit of the IgE receptor (40%) or to IgE itself (5%-10%). Bradykinin is the mediator of angioedema in hereditary angioedema types I and II (C1 inhibitor [INH] deficiency) and the newly described type III disorder some of which are caused bya mutation involving factor XII. Acquired C1 INH deficiency presents in a similar fashion to the hereditary disorder and is due either toC1 INH depletion by circulating immune complexes or to an IgG antibody directed to C1 INH. Although each of these causes excessive bradykinin formation because of activation of the plasma bradykinin-forming pathway, the angioedema due to angiotensin-converting enzyme inhibitors is caused by excessive bradykinin levels due to inhibition of bradykinin degradation. Idiopathic angioedema (ie, pathogenesis unknown) may be histaminergic, that is, caused by mast cell degranulation with histamine release, or nonhistaminergic. The mediator pathways in the latter case are yet to be defined. A minority may be associated with the same autoantibodies associated with chronic urticaria. Angioedema that is likely to be life threatening (laryngeal

  20. Hereditary angioedema: quality of life in Brazilian patients

    Gomide, Maria Abadia Consuelo M S; Eliana Toledo; Solange Oliveira Rodrigues Valle; Campos, Regis A.; Alfeu T. França; Nieves Prior Gomez; Heitor Franco Andrade Jr.; Teresa Caballero; Grumach, Anete S.

    2013-01-01

    OBJECTIVE: Hereditary angioedema is a serious medical condition caused by a rare autosomal dominant genetic disorder and it is associated with deficient production or dysfunction of the C1 esterase inhibitor. In most cases, affected patients experience unexpected and recurrent crises of subcutaneous, gastrointestinal and laryngeal edema. The unpredictability, intensity and other factors associated with the disease impact the quality of life of hereditary angioedema patients. We evaluated the ...

  1. Hereditary angioedema: classification, pathogenesis, and diagnosis.

    Banerji, Aleena

    2011-01-01

    Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder associated with a deficiency in C1 inhibitor. More than 200 mutations in this gene, located on chromosome 11, have been identified. Although HAE is often inherited, 20-25% of cases are from new spontaneous mutations and they have no family history of swelling. Decreased C1 inhibitor activity leads to inappropriate activation of multiple pathways, including the complement and contact systems and the fibrinolysis and coagulation systems. Reduced C1 inhibitor activity results in increased activation of plasma kallikrein-kinin system proteases and increased bradykinin levels. Bradykinin is felt to be the main mediator of symptoms in HAE. Patients with HAE have recurrent episodes of swelling of the extremities, abdomen, face, and upper airway. Angioedema involving the gastrointestinal tract can lead to intestinal wall edema, which results in abdominal pain, nausea, vomiting, and diarrhea. Laryngeal swelling is life-threatening and may lead to asphyxia. Common triggers of an attack include trauma, stress, infection, menstruation, oral contraceptives, hormone replacement therapy, and angiotensin-converting enzyme inhibitors. Laboratory testing including C4, C1 inhibitor level, and function is needed to confirm or rule out the diagnosis of HAE. The treatment of HAE has improved significantly in recent years with the availability of several safe and effective therapies. Several consensus guidelines have been created to further assist in the management of HAE patients. This review will provide an update on the classification, pathophysiology, clinical presentation, and diagnosis of HAE. PMID:22221432

  2. Icatibant in hereditary angioedema: news and challenges.

    Bouillet, Laurence

    2011-05-01

    Hereditary angioedema (HAE) is a rare condition. Its prognosis depends on whether there is laryngeal involvement with a risk of asphyxia, which is present in 25% of such cases. Improved understanding of the pathophysiology of this disease has resulted in the development of targeted therapies including icatibant, which acts as an antagonist at bradykinin B2 receptors. This agent has been shown to be effective in the treatment of attacks of HAE in three Phase III randomized double-blind published studies. Efficacy data have been collected in all types of attack: cutaneous, abdominal and laryngeal. Safety data are also encouraging. Icatibant is administered subcutaneously, with the potential for patients to self-administer. In the future, this therapy may offer increased independence for HAE patients. PMID:21595592

  3. Recent developments in the treatment of acute abdominal and facial attacks of hereditary angioedema: focus on human C1 esterase inhibitor.

    Cardona, Lourdes Pastó; Bellfill, Ramon Lleonart; Caus, Joaquim Marcoval

    2010-01-01

    Hereditary angioedema (HAE) is a potentially fatal genetic disorder typified by a deficiency (type I) or dysfunction (type II) of the C1-inhibitor (C1-INH) and characterized by swelling of the extremities, face, trunk, abdominal viscera, and upper airway. Type III is normal estrogen-sensitive C1-INH HAE. Bradykinin, the main mediator of HAE, binds to endothelial B2 receptors, increasing vascular permeability and resulting in edema. HAE management includes short- and long-term prophylaxis. For treating acute episodes, C1-INH concentrate is recommended with regression of symptoms achieved in 30-90 min. Infusions of 500-1000 U have been used in Europe for years. Two plasma-derived C1-INH concentrates have been licensed recently in the United States: Berinert(®) for treating acute attacks and Cinryze(®) for prophylaxis in adolescent/adult patients. A recombinant C1-INH that is being considered for approval (conestat alfa) exhibited significant superiority versus placebo. Ecallantide (Kalbitor(®)) is a selective kallikrein inhibitor recently licensed in the United States for treating acute attacks in patients aged >16 years. It is administered in three 10-mg subcutaneous injections with the risk of anaphylactic reactions. Icatibant (Firazyr(®)) is a bradykinin B2 receptor competitor. It is administered subcutaneously as a 30-mg injection and approved in Europe but not in the United States. PMID:23776358

  4. Membranous nephropathy in a patient with hereditary angioedema: a case report

    Majoni Sandawana W

    2008-10-01

    Full Text Available Abstract Introduction Hereditary angioedema is the commonest inherited disorder of the complement system and has been associated with several immune glomerular diseases. A case of nephrotic syndrome and renal impairment due to idiopathic membranous glomerulonephritis in a patient with hereditary angioedema has not been described before. Case presentation We present the first reported case of the association of membranous nephropathy and hereditary angioedema in a 43-year-old male Caucasian patient who presented with acute intestinal angioedema, hypertension, acute pancreatitis, renal impairment and generalised body swelling due to severe nephrotic syndrome. We present the challenges involved in the clinical management of the patient. Conclusion This patient's presentation with severe nephrotic syndrome, renal impairment and hypertension required aggressive treatment of the membranous nephropathy given the high risk for progression to end stage renal failure. The contraindication to angiotensin converting enzyme inhibitors and angiotensin II receptor blockers in this patient, the lack of published evidence on the use of alkylating agents and other immunosuppressive agents in patients with hereditary angioedema and the lack of published data on the management of similar cases presented a clinical challenge in this patient's management.

  5. Acute allergic angioedema of upper lip

    Kavitha Mahendran

    2016-01-01

    Full Text Available Mishaps can occur during dental procedures, some owing to inattention to detail and others are totally unpredictable. They usually include anaphylaxis or allergic reactions to materials used for restorative purposes or drugs such as local anesthetics. A patient reported to our department with moderate dental fluorosis, and the treatment was planned with indirect composite veneering. During the procedure while cementation acute allergic reaction occurred, the specific cause could not be identified after allergic testing. During the procedure while cementationacute allergic angioedema of upper lip. Anaphylaxis, urticaria, allergy, hereditary atopic eczema, cellulitis, cheilitis granulomatosa, and cheilitis glandularis. The patient was reassured and given prednisolone 10 mg and cetirizine 10 mg orally, once daily for 3 days after which the symptoms subsided. This paper will discuss the pathogenesis, classification, identification, and management of angioedema during dental procedures.

  6. Acute allergic angioedema of upper lip

    Mahendran, Kavitha; Padmini, Govindasway; Murugesan, Ramesh; Srikumar, Arthiseethalakshmi

    2016-01-01

    Mishaps can occur during dental procedures, some owing to inattention to detail and others are totally unpredictable. They usually include anaphylaxis or allergic reactions to materials used for restorative purposes or drugs such as local anesthetics. A patient reported to our department with moderate dental fluorosis, and the treatment was planned with indirect composite veneering. During the procedure while cementation acute allergic reaction occurred, the specific cause could not be identified after allergic testing. During the procedure while cementationacute allergic angioedema of upper lip. Anaphylaxis, urticaria, allergy, hereditary atopic eczema, cellulitis, cheilitis granulomatosa, and cheilitis glandularis. The patient was reassured and given prednisolone 10 mg and cetirizine 10 mg orally, once daily for 3 days after which the symptoms subsided. This paper will discuss the pathogenesis, classification, identification, and management of angioedema during dental procedures. PMID:27217646

  7. Acute allergic angioedema of upper lip.

    Mahendran, Kavitha; Padmini, Govindasway; Murugesan, Ramesh; Srikumar, Arthiseethalakshmi

    2016-01-01

    Mishaps can occur during dental procedures, some owing to inattention to detail and others are totally unpredictable. They usually include anaphylaxis or allergic reactions to materials used for restorative purposes or drugs such as local anesthetics. A patient reported to our department with moderate dental fluorosis, and the treatment was planned with indirect composite veneering. During the procedure while cementation acute allergic reaction occurred, the specific cause could not be identified after allergic testing. During the procedure while cementationacute allergic angioedema of upper lip. Anaphylaxis, urticaria, allergy, hereditary atopic eczema, cellulitis, cheilitis granulomatosa, and cheilitis glandularis. The patient was reassured and given prednisolone 10 mg and cetirizine 10 mg orally, once daily for 3 days after which the symptoms subsided. This paper will discuss the pathogenesis, classification, identification, and management of angioedema during dental procedures. PMID:27217646

  8. Rhucin, a recombinant C1 inhibitor for the treatment of hereditary angioedema and cerebral ischemia.

    Longhurst, Hilary

    2008-03-01

    Pharming NV and Esteve are developing Rhucin, a recombinant human C1 esterase inhibitor. Rhucin is currently undergoing phase III clinical trials in North America and is awaiting regulatory approval in Western Europe for the treatment of prophylactic and acute hereditary angioedema. Pharming is also investigating Rhucin for the potential treatment of cerebral ischemic injury. PMID:18311668

  9. Pathogenesis and laboratory diagnosis of hereditary angioedema.

    Zuraw, Bruce L; Christiansen, Sandra C

    2009-01-01

    Hereditary angioedema (HAE) was first described in the 19th century. Over the past 50 years, many details of the pathophysiology and molecular biology of HAE have been elucidated. Two types of HAE, type I and type II, result from mutations in the gene for the broad-spectrum protease inhibitor C1 inhibitor (C1INH). Type I HAE is characterized by low antigenic and functional C1INH levels and type II HAE has normal antigenic but low functional C1INH levels. Type III HAE, by contrast, has normal antigenic and functional C1INH levels. In some families, type III HAE has been linked to mutations in Hageman factor. C1INH is the primary inhibitor of the complement proteases C1r and C1s as well as the contact system proteases activated Hageman factor (coagulation factor XIIa and XIIf) and plasma kallikrein. It is also an inhibitor of plasmin and coagulation factor XIa. The primary mediator of swelling in HAE has now been unequivocally shown to be bradykinin, generated from activation of the plasma contact system. The knowledge gained concerning the underlying mechanisms of the different types of HAE allow the clinician to approach the laboratory diagnosis with confidence and provides opportunities for novel therapeutic strategies. PMID:19843402

  10. Anaesthetic management of a patient with hereditary angioedema

    Nergis Ataol

    2015-12-01

    Full Text Available Hereditary angioedema is a rare autosomal dominant disorder caused by reduced activity of the C1 esterase inhibitor. Patients with hereditary angioedema are clinically characterized by recurrent episodes of swelling of the extremities, face, trunk, airways and abdominal organs. Attacks may occur either spontaneously or following trauma, stress, surgery, infections and hormonal fluctuations. The most common cause of death is asphyxia related to laryngeal edema. Giving C1 esterase inhibitor is the most effective method of treatment. Also fresh frozen plasma, androgen steroids, quinine pathway inhibitors, antifibrinolytics and bradykinin receptor antagonists can be used as treatment. In this paper, the anesthetic management of a patient with hereditary angioedema undergoing inguinal hernia repair surgery is reported.

  11. Treatment of hereditary angioedema with plasma-derived C1 inhibitor

    Michael J Prematta

    2008-08-01

    Full Text Available Michael J Prematta, Tracy Prematta, Timothy J CraigSection of Allergy and Immunology, Penn State University, Milton S. Hershey Medical Center, PA, USABackground: Plasma-derived C1 inhibitor (C1-INH concentrate is a treatment option for acute hereditary angioedema (HAE attacks and is considered the standard-of-care in many countries, although it is not yet available in the United States. Studies are still being conducted to establish its safety and efficacy as required by the FDA.Objective: To review the medical literature to determine if C1-INH concentrate is a safe and effective treatment for acute HAE attacks.Methods: The following keywords were searched in PubMed and OVID: C1 esterase inhibitor, C1-inhibitor, C1 inhibitor, and hereditary angioedema treatment. English-language articles were searched from 1966 to the present to look for studies demonstrating the efficacy and the safety of C1-INH concentrate.Results: The English-language literature search revealed several studies showing significantly improved relief of HAE symptoms with the administration of C1-INH concentrate – many studies demonstrated some improvement of symptoms within 30 minutes. Side effects have been similar to placebo, and no proven cases of viral transmission have occurred in over 20 years.Conclusion: C1-INH concentrate appears to be a very safe and effective treatment option for HAE.Keywords: hereditary angioedema, c1 inhibitor, c1 esterase inhibitor, hereditary angioedema treatment

  12. Hereditary angioedema: New therapeutic options for a potentially deadly disorder

    Eidelman Frank J

    2010-05-01

    Full Text Available Abstract Although the biochemistry of hereditary angioedema (HAE is fairly well understood today, the lag in diagnosis of a decade or more suggests that clinicians have low awareness of this disease. This lag in diagnosis and hence treatment certainly stems from the rarity and complexity of the presentation which can be easily mistaken for allergic and non-allergic reactions alike. The symptoms of the disease include acute swelling of any or multiple parts of the body. The attacks may be frequent or rare, and they may vary substantially in severity, causing stomach discomfort or periorbital swelling in mild cases and hypovolemic shock due to abdominal fluid shift or asphyxiation in the most severe cases. Given that these patients are at significant risk for poor quality of life and death, greater awareness of this disease is needed to ensure that newly available, effective medications are used in these patients. These new medications represent significant advances in HAE therapy because they are targeted at the plasma cascades implicated in the pathophysiology of this disease. The clinical presentation of HAE, overlapping symptoms with other angioedemas, and available therapies are reviewed.

  13. Hereditary Angioedema: Three Cases Report, Members of the Same Family

    Alexandros Kolokotronis

    2010-01-01

    Full Text Available Background: This current clinical case report highlights three cases of Hereditary angioedema (HAE patients who are all members of the same family (father and his two daughters. The father has C1–INH deficiency, while his daughters have low C1–INH levels: the first possesses only 10% function and the second has low C1–INH level with 0% function. Of note, the second daughter was discovered to have HAE at the age of 2, thus making her the youngest known HAE case report in the English literature.Methods: Assess the efficacy of administration of C1-INH before dental operation as regards the prevention of HAE episode, when total or partial C1-INH deficiency exists.Results: Acute angioedema leading to laryngeal oedema is a possibly fatal complication for HAE patients undergoing dental procedures. Use of both short-term and long-term HAE prophylaxis prior to dental operations might be life saving for those patients.Conclusions: Prevention and early recognition of potential laryngeal oedema that can occur as a complication of dental procedures may be lifesaving for HAE patients.

  14. Hereditary angio-edema involving the gastrointestinal tract: CT findings

    We report a case of hereditary angio-edema in a young man presenting with recurrent abdominal pain for many years. The diagnosis was suspected on the basis of abdominal CT performed during an abdominal attack and was then confirmed by the measurement of serum concentration of C1 esterase inhibitor (C1-INH). To our knowledge, this is the first case reported of the hereditary form of angio-edema with isolated abdominal pain and in which the diagnosis was suggested by abdominal CT findings. (orig.)

  15. [Hereditary angioedema in childhood. Diagnosis and therapeutic challenges].

    Pagnier, Anne

    2015-01-01

    Hereditary angioedema is a rare disease. In case of laryngeal edema or chronic abdominal pains, diagnosis is difficult in childhood because numerous differential diagnoses possibilities are to be considered. The diagnosis of hereditary angioedema with normal C1Inh (type III) is also a challenge because it is based only on clinical features. Important school absenteeism can be due to recurrent abdominal attacks. Early diagnosis, specific management, and therapeutic education are necessary for improvement of quality of life. Actually, subcutaneous treatment is not yet available for children. Studies are going on. In the meantime, C1Inh concentrate intravenous administration must be available for children quickly and safely. PMID:25511651

  16. Diagnosis and treatment of hereditary angioedema.

    Canonica, G W; Rossi, O

    2012-09-01

    Hereditary angioedema (HAE) is a rare autosomal dominant disorder affecting approximately 1 in 50000 persons. It causes frequent attacks of non-pitting, non-pruritic edema without urticaria, usually of the skin of the extremities, gastrointestinal tract, and upper airways. Gastrointestinal attacks may cause severe pain, and attacks in the laryngeal region may lead to asphyxiation and death. HAE usually begins in childhood or adolescence and persists throughout life. The majority of HAE cases are caused by mutations that result in low levels of functional C1-inhibitor (C1-INH), a serine protease inhibitor that plays regulatory roles in the contact, complement, and fibrinolytic systems. Low C1-INH function results in overproduction of bradykinin, the primary cause of HAE symptoms. Type I HAE is characterized by low levels of functional C1-INH, whereas type II HAE is characterized by normal levels of dysfunctional C1-INH. A third type of HAE has a similar presentation, but is not due to C1-INH deficiency or impairment. Some patients with type III HAE carry mutations in the coagulation factor XII gene that do not alter factor XII plasma levels but markedly increase its activity. HAE is often undiagnosed or misdiagnosed, sometimes leading to inappropriate treatment that may include surgery. HAE should be suspected in any patient who presents with repeated attacks of cutaneous edema without urticaria or recurrent unexplained abdominal pain. Diagnosis requires laboratory testing of complement levels. HAE requires disease-specific treatment with agents that increase functional C1-INH levels and/or reduce the production or activity of bradykinin. These treatments include C1-INH concentrates, icatibant, ecallantide, and attenuated androgens. HAE severely reduces patients' quality of life, which makes supportive care an essential part of the treatment program. PMID:22801442

  17. Hereditary angioedema: what the gastroenterologist needs to know

    Ali MA

    2014-11-01

    Full Text Available M Aamir Ali, Marie L Borum Division of Gastroenterology and Liver Diseases, George Washington University, Washington, DC, USA Abstract: Up to 93% of patients with hereditary angioedema (HAE experience recurrent abdominal pain. Many of these patients, who often present to emergency departments, primary care physicians, general surgeons, or gastroenterologists, are misdiagnosed for years and undergo unnecessary testing and surgical procedures. Making the diagnosis of HAE can be challenging because symptoms and attack locations are often inconsistent from one episode to the next. Abdominal attacks are common and can occur without other attack locations. An early, accurate diagnosis is central to managing HAE. Unexplained abdominal pain, particularly when accompanied by swelling of the face and extremities, suggests the diagnosis of HAE. A family history and radiologic imaging demonstrating edematous bowel also support an HAE diagnosis. Once HAE is suspected, C4 and C1 esterase inhibitor (C1-INH laboratory studies are usually diagnostic. Patients with HAE may benefit from recently approved specific treatments, including plasma-derived C1-INH or recombinant C1-INH, a bradykinin B2-receptor antagonist, or a kallikrein inhibitor as first-line therapy and solvent/detergent-treated or fresh frozen plasma as second-line therapy for acute episodes. Short-term or long-term prophylaxis with nanofiltered C1-INH or attenuated androgens will prevent or reduce the frequency and severity of episodes. Gastroenterologists can play a critical role in identifying and treating patients with HAE, and should have a high index of suspicion when encountering patients with recurrent, unexplained bouts of abdominal pain. Given the high rate of abdominal attacks in HAE, it is important for gastroenterologists to appropriately diagnose and promptly recognize and treat HAE, or refer patients with HAE to an allergist. Keywords: hereditary angioedema, abdominal pain, diagnosis

  18. The prophylactic use of C1 inhibitor in hereditary angioedema patients undergoing invasive surgical procedures: a retrospective study

    Gavigan, Geneviève; Yang, William H; Santucci, Stephanie; Harrison, Rachel; Karsh, Jacob

    2014-01-01

    Background Hereditary Angioedema (HAE) is a rare autosomal dominant condition characterized by episodic angioedema, which may be triggered by invasive procedures and surgery. C1 inhibitor (C1 INH) was approved in the United States and Canada in 2009 and 2010, respectively, for the treatment of acute attacks. Most recently in April 2013, it was approved in Europe for short-term prophylaxis (STP), prior to medical, dental, or surgical procedures, to prevent HAE attacks in both children and adul...

  19. Hereditary angioedema: epidemiology, management, and role of icatibant

    Ghazi A

    2013-05-01

    Full Text Available Aasia Ghazi, J Andrew GrantUniversity of Texas Medical Branch, Division of Allergy and Clinical Immunology, Galveston, TX, USAAbstract: Hereditary angioedema (HAE is an autosomal dominant, potentially life-threatening condition, manifesting as recurrent and self-limiting episodes of facial, laryngeal, genital, or peripheral swelling with abdominal pain secondary to intra-abdominal edema. The estimated prevalence of HAE in the general population is one individual per 50,000, with reported ranges from 1:10,000 to 1:150,000, without major sex or ethnic differences. Various treatment options for acute attacks and prophylaxis of HAE are authorized and available in the market, including plasma-derived (Berinert®, Cinryze®, and Cetor® and recombinant (Rhucin® and Ruconest™ C1 inhibitors, kallikrein inhibitor-ecallantide (Kalbitor®, and bradykinin B2 receptor antagonist-icatibant (Firazyr®. Some of these drugs are used only to treat HAE attacks, whereas others are only approved for prophylactic therapies and all of them have improved disease outcomes due to their different mechanisms of action. Bradykinin and its binding to B2 receptor have been demonstrated to be responsible for most of the symptoms of HAE. Thus icatibant (Firazyr®, a bradykinin B2 receptor antagonist, has proven to be an effective and more targeted treatment option and has been approved for the treatment of acute attacks of HAE. Rapid and stable relief from symptoms of cutaneous, abdominal, or laryngeal HAE attacks has been demonstrated by 30 mg of icatibant in Phase III clinical trials. Self-resolving mild to moderate local site reactions after subcutaneous injection of icatibant were observed. Icatibant is a new, safe, and effective treatment for acute attacks of HAE. HAE has been reported to result in enormous humanistic burden to patients, affecting both physical and mental health, with a negative impact on education, career, and work productivity, and with substantial

  20. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    Bowen Tom; Cicardi Marco; Farkas Henriette; Bork Konrad; Longhurst Hilary J; Zuraw Bruce; Aygoeren-Pürsün Emel; Craig Timothy; Binkley Karen; Hebert Jacques; Ritchie Bruce; Bouillet Laurence; Betschel Stephen; Cogar Della; Dean John

    2010-01-01

    Abstract Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management...

  1. 2010 international consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    Bowen, Tom; Cicardi, Marco; Farkas, Henriette; Bork, Konrad; Longhurst, Hilary J; Zuraw, Bruce; Aygören-Pürsün, Emel; Craig, Timothy; Binkley, Karen; Hebert, Jacques; Ritchie, Bruce; Bouillet, Laurence; Betschel, Stephen; Cogar, Della; Dean, John

    2010-01-01

    Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hered...

  2. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    Bowen, Tom; Cicardi, Marco; Farkas, Henriette; Bork, Konrad; Longhurst, Hilary J; Zuraw, Bruce; Aygoeren-Pürsün, Emel; Craig, Timothy; Binkley, Karen; Hebert, Jacques; Ritchie, Bruce; Bouillet, Laurence; Betschel, Stephen; Cogar, Della; Dean, John

    2010-01-01

    Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hered...

  3. Angioedema

    Kaplan, Allen P

    2008-01-01

    Angioedema can be caused by either mast cell degranulation or activation of the kallikrein-kinin cascade. In the former case, angioedema can be caused by allergic reactions caused by immunoglobulin E (IgE)-mediated hypersensitivity to foods or drugs that can also result in acute urticaria or a more generalized anaphylactic reaction. Nonsteroidal anti-inflammatory drugs (cyclooxygenase 1 inhibitors, in particular) may cause angioedema with or without urticaria, and leukotrienes may have a part...

  4. Management of hereditary angioedema in pediatric patients.

    Farkas, Henriette; Varga, Lilian; Széplaki, Gábor; Visy, Beáta; Harmat, George; Bowen, Tom

    2007-09-01

    Hereditary angioneurotic edema is a rare disorder caused by the congenital deficiency of C1 inhibitor. Recurring angioedematous paroxysms that most commonly involve the subcutis (eg, extremities, face, trunk, and genitals) or the submucosa (eg, intestines and larynx) are the hallmarks of hereditary angioneurotic edema. Edema formation is related to reduction or dysfunction of C1 inhibitor, and conventional therapy with antihistamines and corticosteroids is ineffective. Manifestations occur during the initial 2 decades of life, but even today there is a long delay between the onset of initial symptoms and the diagnosis of hereditary angioneurotic edema. Although a variety of reviews have been published during the last 3 decades on the general management of hereditary angioneurotic edema, little has been published regarding management of pediatric hereditary angioneurotic edema. Thus, we review our experience and published data to provide an approach to hereditary angioneurotic edema in childhood. PMID:17724112

  5. Cardiac arrest due to airway obstruction in hereditary angioedema.

    Fuse, Takashi; Nakada, Taka-aki; Taniguchi, Masashi; Mizushima, Yasuaki; Matsuoka, Tetsuya

    2015-12-01

    Hereditary angioedema (HAE) is a rare genetic disease caused by a deficiency of functional C1 esterase inhibitor that causes swelling attacks in various body tissues. We hereby report a case of out-of-hospital cardiac arrest due to airway obstruction in HAE. Cutaneous swelling and abdominal pain attacks caused by gastrointestinal wall swelling are common symptoms in HAE, whereas laryngeal swelling is rare. Emergency physicians may have few chances to experience cases of life-threatening laryngeal edema resulting in a delay from symptom onset to the diagnosis of HAE. Hereditary angioedema is diagnosed by performing complement blood tests. Because safe and effective treatment options are available for the life-threatening swellings in HAE, the diagnosis potentially reduces the risk of asphyxiation in patients and their blood relatives. PMID:25913082

  6. [Prophylactic use of icatibant before tracheal intubation of a patient with hereditary angioedema type III. (A literature review of perioperative management of patients with hereditary angioedema type III)].

    Iturri Clavero, F; González Uriarte, A; Tamayo Medel, G; Gamboa Setién, P M

    2014-01-01

    Type III hereditary angioedema is a rare familial disorder that has recently been described as a separate condition. Triggers for episodes of angioedema include surgery, dental procedures, and tracheal intubation maneuvers. Since episodes affecting the upper airway are potentially life-threatening, prophylactic treatment is recommended in these situations. The use of icatibant (Firazyr(®)), for prevention of angioedema prior to tracheal intubation, is reported in a patient with type iii hereditary angioedema. A literature review on the anesthetic management of this condition was conducted. PMID:24931134

  7. Hereditary angioedema type III (estrogen-dependent) report of three cases and literature review.

    Miranda, Amanda Rodrigues; Ue, Ana Paula Fusel de; Sabbag, Dominique Vilarinho; Furlani, Wellington de Jesus; Souza, Patrícia Karla de; Rotta, Osmar

    2013-01-01

    In this article, three cases of hereditary angioedema (HAE) type III (estrogen-dependent or with normal C1 inhibitor) are reported. The HAE was initially described in women of the same family in association with high-leveled estrogenic conditions such as the use of oral contraceptives and pregnancy. There is no change in the C1 inhibitor as happens in other types of hereditary angioedema, and mutations are observed in the encoding gene of the XII factor of coagulation in several patients. The current diagnosis is mainly clinical and treatment consists in the suspension of the triggering factors and control of acute symptoms. A brief review of physiopathology, clinical features, genetic alterations and treatment are also presented. PMID:24068129

  8. Hereditary angioedema: quality of life in Brazilian patients

    Maria Abadia Consuelo M. S. Gomide

    2013-01-01

    Full Text Available OBJECTIVE: Hereditary angioedema is a serious medical condition caused by a rare autosomal dominant genetic disorder and it is associated with deficient production or dysfunction of the C1 esterase inhibitor. In most cases, affected patients experience unexpected and recurrent crises of subcutaneous, gastrointestinal and laryngeal edema. The unpredictability, intensity and other factors associated with the disease impact the quality of life of hereditary angioedema patients. We evaluated the quality of life in Brazilian hereditary angioedema patients. METHODS: Patients older than 15 years with any severity of hereditary angioedema and laboratory confirmation of C1 inhibitor deficiency were included. Two questionnaires were used: a clinical questionnaire and the SF-36 (a generic questionnaire. This protocol was approved by the Ethics Committee of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. RESULTS: The SF-36 showed that 90.4% (mean of all the patients had a score below 70 and 9.6% had scores equal to or higher than 70. The scores of the eight dimensions ranged from 51.03 to 75.95; vitality and social aspects were more affected than other arenas. The internal consistency of the evaluation was demonstrated by a Cronbach's alpha value above 0.7 in seven of the eight domains. CONCLUSIONS: In this study, Brazilian patients demonstrated an impaired quality of life, as measured by the SF-36. The most affected domains were those related to vitality and social characteristics. The generic SF-36 questionnaire was relevant to the evaluation of quality of life; however, there is a need for more specific instruments for better evaluation.

  9. Hereditary angioedema type I: a case report

    Francisca Muñoz Peralta

    2016-03-01

    Full Text Available El angioedema hereditario es una enfermedad rara, de gran heterogeneidad en los síntomas, manifestándose con edema a nivel cutáneo, mucosa gastrointestinal y de laringe/faringe. Aunque existen tres variedades, el tipo I es el más frecuente y es provocado por una deficiencia en la síntesis del complemento C1 inhibidor. La gravedad de la clínica, junto a la baja prevalencia de la enfermedad y la necesidad de un tratamiento específico, hacen que el diagnóstico y tratamiento de dicha patología sea aún una asignatura pendiente para el médico de familia en atención primaria. Presentamos el caso de un adolescente varón con déficit de α-1 antitripsina desde los seis meses de edad, con aparición de angioedemas en piernas y brazos a los 11 años, diagnosticado de angioedema hereditario tipo I un año después. El diagnóstico definitivo de la enfermedad permitió instaurar un tratamiento adecuado a su patología, que consiste en la prevención de brotes que puedan comprometer la vida del paciente y, en el caso de que aparezcan, en la administración del complemento C1 inhibidor.

  10. Growth factors and IL-17 in hereditary angioedema.

    Salemi, M; Mandalà, V; Muggeo, V; Misiano, G; Milano, S; Colonna-Romano, G; Arcoleo, F; Cillari, E

    2016-05-01

    Hereditary angioedema (HAE) is a rare autosomal dominant disorder, due to C1-inhibitor deficiency, which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways which are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis in basal and crisis state and n = 19 healthy subjects. The samples were tested for IL-17, FGFb, G-CSF and GM-CSF, using Bio-plex kit. Data analysis was performed via nonparametric Spearman's correlations and two sets of linear mixed models. When comparing HAE subjects during basal and crisis states, we found out significantly (i.e., p value <0.05) higher values in crisis states rather than in basal states for the three growth factors and cytokine IL-17. When comparing healthy subjects versus HAE patients at basal state, we found out significantly higher values in HAE subjects only for GM-CSF, FGFb and IL-17, but not for G-CSF. In HAE patients, there is a connection between IL-17 and growth factors. The low-grade inflammation in absence of attacks is demonstrated by constant higher amount of IL-17, FGFb and GM-CSF with respect to healthy patients. This could indicate that in this disease there is a level of activation that maintains the system in a "tick-over state," that can be activate by several stimuli that are able to induce a increase in inflammatory mediators during the acute attack. PMID:25773165

  11. Hereditary Angioedema in Swedish Adults: Report From the National Cohort.

    Nordenfelt, Patrik; Nilsson, Mats; Björkander, Janne; Mallbris, Lotus; Lindfors, Anders; Wahlgren, Carl-Fredrik

    2016-04-12

    Hereditary angioedema (HAE) is rare, disabling and sometimes life-threatening. The aim of this study is to describe its prevalence, symptomatology and treatment in Sweden. A total of 146 patients were identified; 110 adults and 36 children with HAE type I (n = 136) or II (n = 10), giving a minimal HAE prevalence of 1.54/100,000. All patients received a written questionnaire followed by a structured telephone interview. This report focuses on the 102 adults who responded. Females reported 19 attacks in the previous year vs. 9 for males (p < 0.01), and females reported 10 days of sick leave vs. 4 days for males (p < 0.05). For all treated acute attacks, plasma-derived C1-inhibitor concentrate (pdC1INH) (used in 27% of patients) had a good effect. For maintenance treatment, 43% used attenuated androgens and 8% used pdC1INH, which reduced their attack rate by more than 50%. In conclusion, the minimal HAE prevalence in Sweden was 1.54/100,000. HAE affected females more severely. Attenuated androgens and pdC1INH had a good effect on preventing attacks. PMID:26540175

  12. Management of hereditary angioedema in pregnant women: a review

    Caballero T

    2014-09-01

    Full Text Available Teresa Caballero,1,2 Julio Canabal,1 Daniela Rivero-Paparoni,1 Rosario Cabañas1 1Hospital La Paz Institute for Health Research, (IdiPaz 2Biomedical Research Network on Rare Diseases-U754 (CIBERER, Madrid, Spain Abstract: Three types of hereditary angioedema (HAE have been described: two are due to C1 inhibitor (C1-INH deficiency (C1-INH-HAE types I and II and one is characterized by normal C1-INH (nC1-INH-HAE. The management of pregnancy in patients with HAE is often a clinical challenge owing to potential worsening of the disease in relation to the physiological increase in estrogens and the limited treatment options. This review addresses the potential influence of pregnancy on the clinical severity of hereditary angioedema and the management of this disease during pregnancy with currently available treatments. Keywords: hereditary angioedema, pregnancy, female, treatment, C1 inhibitor concentrate, tranexamic acid

  13. Self-administration of intravenous C1-inhibitor therapy for hereditary angioedema and associated quality of life benefits

    Bygum, Anette; Andersen, Klaus Ejner; Mikkelsen, Carsten Sauer

    2009-01-01

    Hereditary angioedema (HAE) is often debilitating with a serious effect on quality of life (QOL). Treatment of acute HAE attacks is usually with C1 esterase inhibitor (C1-INH) concentrates; however, treatment can be delayed by patients' travel time for attending emergency units. We assessed the...

  14. Hereditary angioedema with normal C1-INH (HAE type III).

    Riedl, Marc A

    2013-01-01

    Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH), also known as HAE type III, is a familial condition only clinically recognized within the past three decades. Similar to HAE from C1-INH deficiency (HAE types I and II), affected individuals experience unpredictable angioedema episodes of the skin, gastrointestinal tract, and airway. Unique clinical features of HAE with normal C1-INH include the predominance of affected women, frequent exacerbation by estrogen, and a prominence of angioedema that involves the face and oropharynx. The underlying pathophysiology of HAE with normal C1-INH is poorly understood, but indirect evidence points to contact pathway dysregulation with bradykinin-mediated angioedema. Currently, evaluation is complicated by a lack of confirmatory laboratory testing such that clinical criteria must often be used to make the diagnosis of HAE with normal C1-INH. Factor XII mutations have been identified in only a minority of persons affected by HAE with normal C1-INH, limiting the utility of such analysis. To date, no controlled clinical studies have examined the efficacy of therapeutic agents for HAE with normal C1-INH, although published evidence supports frequent clinical benefit with medications shown effective in HAE due to C1-INH deficiency. PMID:24565612

  15. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    Bowen, Tom; Cicardi, Marco; Farkas, Henriette;

    2010-01-01

    ABSTRACT: BACKGROUND: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 ...

  16. Pediatric hereditary angioedema due to C1-inhibitor deficiency

    Farkas Henriette

    2010-07-01

    Full Text Available Abstract Hereditary angioedema (HAE resulting from the deficiency of the C1 inhibitor (C1-INH is a rare, life-threatening disorder. It is characterized by attacks of angioedema involving the skin and/or the mucosa of the upper airways, as well as the intestinal mucosa. In approximately 50 per cent of cases, clinical manifestations may appear during childhood. The complex management of HAE in pediatric patients is in many respects different from the management of adults. Establishing the diagnosis early, preferably before the onset of clinical symptoms, is essential in cases with a positive family history. Complement studies usually afford accurate diagnosis, whereas molecular genetics tests may prove helpful in uncertain cases. Appropriate therapy, supported by counselling, suitable modification of lifestyle, and avoidance of triggering factors (which primarily include mechanical trauma, mental stress and airway infections in children may spare the patient unnecessary surgery and may prevent mortality. Prompt control of edematous attacks, short-term prophylaxis and intermittent therapy are recommended as the primary means for the management of pediatric cases. Medicinal products currently used for the treatment of children with hereditary angioedema include antifibrinolytics, attenuated androgens, and C1-INH replacement therapy. Current guidelines favour antifibrinolytics for long-term prophylaxis because of their favorable safety profile but efficacy may be lacking. Attenuated androgens administered in the lowest effective dose are another option. C1-INH replacement therapy is also an effective and safe agent for children. Regular monitoring and follow-up of patients are necessary.

  17. Hereditary angioedema in childhood: an approach to management.

    Ebo, Didier G; Verweij, Marjoke M; De Knop, Kathleen J; Hagendorens, Margo M; Bridts, Chris H; De Clerck, Luc S; Stevens, Wim J

    2010-08-01

    Hereditary angioedema (HAE) is an inherited disorder characterized by recurrent, circumscribed, non-pitting, non-pruritic, and rather painful subepithelial swelling of sudden onset, which fades during the course of 48-72 hours, but can persist for up to 1 week. Lesions can be solitary or multiple, and primarily involve the extremities, larynx, face, esophagus, and bowel wall. Patients with HAE experience angioedema because of a defective control of the plasma kinin-forming cascade that is activated through contact with negatively charged endothelial macromolecules leading to binding and auto-activation of coagulation factor XII, activation of prekallikrein to kallikrein by factor XIIa, and cleavage of high-molecular-weight kininogen by kallikrein to release the highly potent vasodilator bradykinin. Three forms of HAE have currently been described. Type I and type II HAE are rare autosomal dominant diseases due to mutations in the C1-inhibitor gene (SERPING1). C1-inhibitor mutations that cause type I HAE occur throughout the gene and result in truncated or misfolded proteins with a deficiency in the levels of antigenic and functional C1-inhibitor. Mutations that cause type II HAE generally involve exon 8 at or adjacent to the active site, resulting in an antigenically intact but dysfunctional mutant protein. In contrast, type III HAE (also called estrogen-dependent HAE) is characterized by normal C1-inhibitor activity. The diagnosis of HAE is suggested by a positive family history, the absence of accompanying pruritus or urticaria, the presence of recurrent gastrointestinal attacks of colic, and episodes of laryngeal edema. Estrogens may exacerbate attacks, and in some patients attacks are precipitated by trauma, inflammation, or psychological stress. For type I and type II HAE, diminished C4 concentrations are highly suggestive for the diagnosis. Further laboratory diagnosis depends on demonstrating a deficiency of C1-inhibitor antigen (type I) in most kindreds

  18. Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment.

    Zeerleder, Sacha; Levi, Marcel

    2016-06-01

    hereditary and acquired C1-inhibitor-dependent angioedema is potentially life threatening and can occur at any age. To date effective therapies for acute and prophylactic treatment are available. PMID:27018196

  19. Diagnosis and screening of patients with hereditary angioedema in primary care

    Henao MP

    2016-05-01

    Full Text Available Maria Paula Henao,1 Jennifer L Kraschnewski,1 Theodore Kelbel,2 Timothy J Craig3 1Department of Medicine, 2Division of Allergy and Immunology, 3Department of Medicine and Pediatrics, Pennsylvania State University College of Medicine at Hershey Medical Center, Hershey, PA, USA Abstract: Hereditary angioedema (HAE is a rare autosomal dominant disease that commonly manifests with episodes of cutaneous or submucosal angioedema and intense abdominal pain. The condition usually presents due to a deficiency of C1 esterase inhibitor (C1-INH that leads to the overproduction of bradykinin, causing an abrupt increase in vascular permeability. A less-understood and less-common form of the disease presents with normal C1-INH levels. Symptoms of angioedema may be confused initially with mast cell-mediated angioedema, such as allergic reactions, and may perplex physicians when epinephrine, antihistamine, or glucocorticoid therapies do not provide relief. Similarly, abdominal attacks may lead to unnecessary surgeries or opiate dependence. All affected individuals are at risk for a life-threatening episode of laryngeal angioedema, which continues to be a source of fatalities due to asphyxiation. Unfortunately, the diagnosis is delayed on average by almost a decade due to a misunderstanding of symptoms and general lack of awareness of the disease. Once physicians suspect HAE, however, diagnostic methods are reliable and available at most laboratories, and include testing for C4, C1-INH protein, and C1-INH functional levels. In patients with HAE, management consists of acute treatment of an attack as well as possible short- or long-term prophylaxis. Plasma-derived C1-INH, ecallantide, icatibant, and recombinant human C1-INH are new treatments that have been shown to be safe and effective in the treatment of HAE attacks. The current understanding of HAE has greatly improved in recent decades, leading to growing awareness, new treatments, improved management

  20. Hereditary angioedema: epidemiology, management, and role of icatibant.

    Ghazi, Aasia; Grant, J Andrew

    2013-01-01

    Hereditary angioedema (HAE) is an autosomal dominant, potentially life-threatening condition, manifesting as recurrent and self-limiting episodes of facial, laryngeal, genital, or peripheral swelling with abdominal pain secondary to intra-abdominal edema. The estimated prevalence of HAE in the general population is one individual per 50,000, with reported ranges from 1:10,000 to 1:150,000, without major sex or ethnic differences. Various treatment options for acute attacks and prophylaxis of HAE are authorized and available in the market, including plasma-derived (Berinert®, Cinryze®, and Cetor®) and recombinant (Rhucin® and Ruconest™) C1 inhibitors, kallikrein inhibitor-ecallantide (Kalbitor®), and bradykinin B2 receptor antagonist-icatibant (Firazyr®). Some of these drugs are used only to treat HAE attacks, whereas others are only approved for prophylactic therapies and all of them have improved disease outcomes due to their different mechanisms of action. Bradykinin and its binding to B2 receptor have been demonstrated to be responsible for most of the symptoms of HAE. Thus icatibant (Firazyr®), a bradykinin B2 receptor antagonist, has proven to be an effective and more targeted treatment option and has been approved for the treatment of acute attacks of HAE. Rapid and stable relief from symptoms of cutaneous, abdominal, or laryngeal HAE attacks has been demonstrated by 30 mg of icatibant in Phase III clinical trials. Self-resolving mild to moderate local site reactions after subcutaneous injection of icatibant were observed. Icatibant is a new, safe, and effective treatment for acute attacks of HAE. HAE has been reported to result in enormous humanistic burden to patients, affecting both physical and mental health, with a negative impact on education, career, and work productivity, and with substantial economic burdens. The timely and proper use of disease-specific treatments could improve patients' quality of life, reduce the disease

  1. Angioedema hereditário: considerações sobre terapia Therapeutic approach of hereditary angioedema

    Kélem de Nardi Chagas

    2004-09-01

    HAE ser causado pelo mesmo defeito e acometer membros da mesma família, diferentes critérios têm sido estabelecidos para o tratamento desses pacientes. Foram indicados diferentes esquemas terapêuticos para HAE e alguns dos pacientes puderam ser seguidos sem terapia medicamentosa.PURPOSE: Hereditary Angioedema was first described by William Osler in 1888 and it is caused by a hereditary or acquired deficiency of C1 esterase inhibitor (C1-INH. Treatment is indicated for acute attacks or prophylaxis of angioedema which occur in the subcutaneous tissue respiratory or gastrointestinal tracts. Treatment includes attenuated androgens, inhibitors of kininogen or plasminogen, like tranexamic acid or e-aminocaproic acid and the administration of C1-INH concentrate. We describe the peculiarities of the treatment chosen for 10 patients (4 families with HAE and their evolution. METHODS: Ten patients (1-38 years old with HAE were diagnosed by clinical history and laboratory evaluation. The following tests were performed for the complement system: C1-INH, C4 and C3 levels and hemolytic assay (CH50 and APH50 for the classic and alternative pathways. Treatment was initiated considering severity of symptoms, age, gender and therapeutic response of the patient. RESULTS: Clinical evaluation showed: 4/10 patients with recurrent subcutaneous edema; 3/10 with previous laryngeal edema and 3/10 with sporadic symptoms. Different severity of symptoms was verified in the same family. The laboratory evaluation detected: low C1-INH levels (10/10; low serum C4 level (8/10; undetectable CH50 (3/10 and low CH50 levels (6/10; low APH50 levels (2/10. Six out of ten patients did not receive any specific treatment and 2 of them had high risk of asphyxia. One adolescent had been controlled with e-aminocaproic acid, one child had been changed from danazol to tranexamic acid, a 30 year old female patient had received oxandrolone and a 38 year old man had been treated with danazol. CONCLUSIONS: Although

  2. Neurofeedback in Hereditary Angioedema: A Single Case Study of Symptom Reduction.

    Burns, Stephanie T

    2015-09-01

    Neurofeedback training was performed consisting of rewarding and encouraging 12-15 Hz brainwaves (SMR), while simultaneously discouraging 4-7 Hz brainwaves (theta) and 22-30 Hz brainwaves (high beta) in the right dorsal posterior quadrant of the brain (T4, P4) for 20 half-hour NFB sessions to determine the impact on cortisol levels, DHEA-S levels, scores on the Symptom Checklist-90-R (SCL-90-R), the quality of life inventory, and acute attack medication usage for a Hereditary Angioedema patient. PMID:25958076

  3. Burden of Illness in Hereditary Angioedema: A Conceptual Model.

    Bygum, Anette; Aygören-Pürsün, Emel; Beusterien, Kathleen; Hautamaki, Emily; Sisic, Zlatko; Wait, Suzanne; Boysen, Henrik B; Caballero, Teresa

    2015-07-01

    The objective of the Hereditary Angioedema Burden of Illness Study in Europe was to assess the real-world experience of hereditary angioedema (HAE) from the patient perspective. Based on open-ended qualitative interviews with 30 patients from Spain, Germany and Denmark, 5 key themes emerged characterizing the impact of HAE on health-related quality of life (HRQoL): (i) unnecessary treatments and procedures, (ii) symptom triggers, (iii) attack impacts, (iv) caregiver impacts, and (v) long-term impacts. Patients for example experience unnecessary medical procedures due to diagnostic delays; anxiety and fear about attacks, and passing HAE to children; reduced work/school productivity; and limited career/educational achievement. Patient caregivers also experience worry and work/activity interruption during the attacks. In conclusion, a conceptual model was developed illustrating the hypothesized relationships among the wide-ranging short- and long-term HRQoL impacts of HAE. These findings can be used to highlight important issues in clinical management, raise awareness of the patients' experience among policymakers and help guide measurement of HRQoL outcomes in future studies in HAE. PMID:25394853

  4. Diagnosis and screening of patients with hereditary angioedema in primary care

    Henao, Maria Paula; Kraschnewski, Jennifer L.; Kelbel, Theodore; Craig, Timothy J.

    2016-01-01

    Hereditary angioedema (HAE) is a rare autosomal dominant disease that commonly manifests with episodes of cutaneous or submucosal angioedema and intense abdominal pain. The condition usually presents due to a deficiency of C1 esterase inhibitor (C1-INH) that leads to the overproduction of bradykinin, causing an abrupt increase in vascular permeability. A less-understood and less-common form of the disease presents with normal C1-INH levels. Symptoms of angioedema may be confused initially wit...

  5. Diagnosis and screening of patients with hereditary angioedema in primary care.

    Henao, Maria Paula; Kraschnewski, Jennifer L; Kelbel, Theodore; Craig, Timothy J

    2016-01-01

    Hereditary angioedema (HAE) is a rare autosomal dominant disease that commonly manifests with episodes of cutaneous or submucosal angioedema and intense abdominal pain. The condition usually presents due to a deficiency of C1 esterase inhibitor (C1-INH) that leads to the overproduction of bradykinin, causing an abrupt increase in vascular permeability. A less-understood and less-common form of the disease presents with normal C1-INH levels. Symptoms of angioedema may be confused initially with mast cell-mediated angioedema, such as allergic reactions, and may perplex physicians when epinephrine, antihistamine, or glucocorticoid therapies do not provide relief. Similarly, abdominal attacks may lead to unnecessary surgeries or opiate dependence. All affected individuals are at risk for a life-threatening episode of laryngeal angioedema, which continues to be a source of fatalities due to asphyxiation. Unfortunately, the diagnosis is delayed on average by almost a decade due to a misunderstanding of symptoms and general lack of awareness of the disease. Once physicians suspect HAE, however, diagnostic methods are reliable and available at most laboratories, and include testing for C4, C1-INH protein, and C1-INH functional levels. In patients with HAE, management consists of acute treatment of an attack as well as possible short- or long-term prophylaxis. Plasma-derived C1-INH, ecallantide, icatibant, and recombinant human C1-INH are new treatments that have been shown to be safe and effective in the treatment of HAE attacks. The current understanding of HAE has greatly improved in recent decades, leading to growing awareness, new treatments, improved management strategies, and better outcomes for patients. PMID:27194914

  6. Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations

    Wagenaar-Bos, Ineke G A; Drouet, Christian; Aygören-Pursun, Emel;

    2008-01-01

    Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of potentially life-threatening angioedema. The most widespread underlying genetic deficiency is a heterozygous deficiency of the serine protease inhibitor C1 esterase inhibitor (C1-Inh). In addition ...

  7. Open-label, multicenter study of self-administered icatibant for attacks of hereditary angioedema

    Aberer, W; Maurer, M; Reshef, A; Longhurst, H; Kivity, S; Bygum, Anette; Caballero, T; Bloom, B; Nair, N; Malbrán, A

    2014-01-01

    Historically, treatment for hereditary angioedema (HAE) attacks has been administered by healthcare professionals (HCPs). Patient self-administration could reduce delays between symptom onset and treatment, and attack burden. The primary objective was to assess the safety of self...

  8. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond.

    Agostoni, Angelo; Aygören-Pürsün, Emel; Binkley, Karen E; Blanch, Alvaro; Bork, Konrad; Bouillet, Laurence; Bucher, Christoph; Castaldo, Anthony J; Cicardi, Marco; Davis, Alvin E; De Carolis, Caterina; Drouet, Christian; Duponchel, Christiane; Farkas, Henriette; Fáy, Kálmán; Fekete, Béla; Fischer, Bettina; Fontana, Luigi; Füst, George; Giacomelli, Roberto; Gröner, Albrecht; Hack, C Erik; Harmat, George; Jakenfelds, John; Juers, Mathias; Kalmár, Lajos; Kaposi, Pál N; Karádi, István; Kitzinger, Arianna; Kollár, Tímea; Kreuz, Wolfhart; Lakatos, Peter; Longhurst, Hilary J; Lopez-Trascasa, Margarita; Martinez-Saguer, Inmaculada; Monnier, Nicole; Nagy, István; Németh, Eva; Nielsen, Erik Waage; Nuijens, Jan H; O'grady, Caroline; Pappalardo, Emanuela; Penna, Vincenzo; Perricone, Carlo; Perricone, Roberto; Rauch, Ursula; Roche, Olga; Rusicke, Eva; Späth, Peter J; Szendei, George; Takács, Edit; Tordai, Attila; Truedsson, Lennart; Varga, Lilian; Visy, Beáta; Williams, Kayla; Zanichelli, Andrea; Zingale, Lorenza

    2004-09-01

    Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder. PMID:15356535

  9. Social costs of icatibant self-administration vs. health professional-administration in the treatment of hereditary angioedema in Spain

    Blasco, Antonio J.; Lázaro, Pablo; Caballero, Teresa; Guilarte, Mar

    2013-01-01

    Background: Icatibant is the only subcutaneous treatment for acute Type I and Type II hereditary angioedema with C1-esterase inhibitor deficiency (HAE-C1-INH) licensed for self-administration in Europe. Aim: To compare the economic impact of two icatibant administration strategies: health professional-administration only (strategy 1) versus including the patient self-administration option (strategy 2). Methods:Economic evaluation model based on the building of a decision tree. Both strategies...

  10. Pediatric Hereditary Angioedema: Onset, Diagnostic Delay, and Disease Severity.

    Christiansen, Sandra C; Davis, Donna K; Castaldo, Anthony J; Zuraw, Bruce L

    2016-09-01

    Hereditary angioedema (HAE) typically presents in childhood. Large gaps remain in our understanding of the natural history of HAE during childhood. We examined age of onset, delay in diagnosis, androgen exposure, and their influence on ultimate disease severity in a large cohort of patients with HAE. Median age of first swelling was 11 years with a median age at diagnosis of 19 years. Earlier onset of symptoms correlated with longer delays in diagnosis (P < .001) and predicted a more severe disease course, including increased number of attacks per year (P = .0009) and hospital admissions (P = .009). Earlier age of onset also significantly correlated with increased perceived HAE severity (P = .0002), negative overall life impact (P < .0001), and use of anabolic androgen. Our observations highlight the importance of early HAE diagnosis and suggest the necessity of a disease management plan once the diagnosis has been made. PMID:26581355

  11. Optimizing hereditary angioedema management through tailored treatment approaches.

    Nasr, Iman H; Manson, Ania L; Al Wahshi, Humaid A; Longhurst, Hilary J

    2016-01-01

    Hereditary angioedema (HAE) is a rare but serious and potentially life threatening autosomal dominant condition caused by low or dysfunctional C1 esterase inhibitor (C1-INH) or uncontrolled contact pathway activation. Symptoms are characterized by spontaneous, recurrent attacks of subcutaneous or submucosal swellings typically involving the face, tongue, larynx, extremities, genitalia or bowel. The prevalence of HAE is estimated to be 1:50,000 without known racial differences. It causes psychological stress as well as significant socioeconomic burden. Early treatment and prevention of attacks are associated with better patient outcome and lower socioeconomic burden. New treatments and a better evidence base for management are emerging which, together with a move from hospital-centered to patient-centered care, will enable individualized, tailored treatment approaches. PMID:26496459

  12. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema

    Bowen Tom

    2010-07-01

    Full Text Available Abstract Background We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. Objective To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010. Methods The Canadian Hereditary Angioedema Network (CHAEN/Réseau Canadien d'angioédème héréditaire (RCAH http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review. Results This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. Conclusions Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management.

  13. Update on laboratory tests for the diagnosis and differentiation of hereditary angioedema and acquired angioedema.

    Frazer-Abel, Ashley; Giclas, Patricia C

    2011-01-01

    The importance of laboratory testing in the diagnosis of hereditary angioedema (HAE) has increased with the advent of new treatment options in recent years. It has been 50 years since HAE was linked to a decrease of C1INH (the inhibitor of complement enzyme, C1 esterase), a link that provided for the first laboratory test available for this disorder. HAE is subdivided into types that can be differentiated only by laboratory testing. The Type I form is characterized by low levels and function of C1INH in the circulation. The Type II form is characterized by normal levels of C1INH, but low function. Sample collection and handling is critical for the functional assays. The serum samples for the functional analysis must be collected, separated, and frozen at less than -60°C within 2 hours of the blood draw. Additionally some suspected Type II patients may benefit from looking closely at what method is used for the functional testing. The acquired forms of angioedema (AAE) can benefit from the same clinical testing, because most are ultimately due to decreased C1INH. Measurement of C1q levels and testing for anti-C1INH autoantibodies can help differentiate AAE from HAE. Diagnostic testing for the third hereditary form, alternately called estrogen-dependent HAE, HAE with Normal C1INH or HAE Type III, still presents challenges, and definitive testing may have to wait until there is a more complete understanding of this mixed group of patients. The next steps will include genetic analysis of C1INH and other proteins involved in HAE. PMID:22195757

  14. Prevalence of autoantibodies in a group of hereditary angioedema patients Prevalência de autoanticorpos em uma população com angioedema hereditário

    Sergio Duarte Dortas Junior

    2012-04-01

    Full Text Available Hereditary Angioedema is a dominantly inherited disease. Routine screening of autoantibodies (AAB is not recommended for individuals with Hereditary Angioedema; however, prevalence of these antibodies in Hereditary Angioedema patients is not well documented. We aim to determine the prevalence of AAB so that individuals at risk of developing autoimmune diseases can be identified. Fifteen patients with Hereditary Angioedema attended at Clementino Fraga Filho University Hospital accepted to participate in this study. Prevalence of AAB was 40%. Our data indicate high prevalence of AAB in patients with Hereditary Angioedema. Large-scale studies should be considered to determine the significance of these AAB in the follow-up care of patients with Hereditary Angioedema.O Angioedema Hereditário é uma doença autossômica dominante. A pesquisa de rotina para autoanticorpos não é recomendada para pacientes com Angioedema Hereditário; entretanto, a prevalência desses anticorpos em pacientes com Angioedema Hereditário não está bem documentada. Objetivamos determinar a prevalência de autoanticorpos para identificar indivíduos sob risco de desenvolver doenças autoimunes. Quinze pacientes com Angioedema Hereditário atendidos no Hospital Universitário Clementino Fraga Filho aceitaram participar do estudo. A prevalência de autoanticorpos foi de 40%. Nossos dados indicam alta prevalência de autoanticorpos em pacientes com Angioedema Hereditário. Estudos de maior escala deveriam ser considerados para determinar a significância desses autoanticorpos no acompanhamento clínico de pacientes com Angioedema Hereditário.

  15. A Family with Hereditary Angioedema Having Been Followed as Familial Mediterranean Fever

    Gülben Sarıcı

    2009-03-01

    Full Text Available Hereditary angioedema is a rare autosomal dominant disorder resulting from the congenital deficiency of functional C1 esterase inhibitor protein. Patients with hereditary angioedema are clinically characterized by recurrent episodes of swelling of the extremities, face, trunk, airways and abdominal viscera. Attacks may occur either spontaneously or following stress or trauma. The disease is usually associated with attacks of abdominal pain. So, patients may apply for this complaint to other clinics rather than dermatology, and may be misdiagnosed and followed for a long time. Therefore hereditary angioedema should be thought in differential diagnosis of patients suffering from abdominal pain. Here in this writing, we describe a family with hereditary angioedema who has been followed as Familial Mediterranean Fever for a long time. The family members complained from swellings which have been occuring in various regions of the body and disappearing spontaneously, and complained from severe abdominal pain, since childhood. These patients have been followed and tried to be treated with the misdiagnosis of Familial Mediterranean Fever for many years. These patients were diagnosed as hereditary angioedema in our clinic, and benefited from danazol treatment

  16. The effect of long-term danazol prophylaxis on liver function in hereditary angioedema?a longitudinal study

    Farkas, Henriette; Czaller, Ibolya; Csuka, Dorottya; Vas, Anikó; Valentin, Szilvia; Varga, Lilian; Széplaki, Gábor; Jakab, László; Füst, George; Prohászka, Zoltán; Harmat, George; Visy, Beata; Karádi, István

    2009-01-01

    Abstract Background Danazol is a drug most widely used for the prophylaxis of hereditary angioedema resulting from the deficiency of the C1-inhibitor. Potential hepatotoxic or liver tumor-inducing side effects of long-term danazol prophylaxis have been investigated during the follow-up of hereditary angioedema patients. Methods Characteristic parameters of liver function (including bilirubin, GOT, GPT, ?GT...

  17. Diagnosis and screening of patients with hereditary angioedema in primary care

    Henao, Maria Paula

    2016-01-01

    Maria Paula Henao,1 Jennifer L Kraschnewski,1 Theodore Kelbel,2 Timothy J Craig3 1Department of Medicine, 2Division of Allergy and Immunology, 3Department of Medicine and Pediatrics, Pennsylvania State University College of Medicine at Hershey Medical Center, Hershey, PA, USA Abstract: Hereditary angioedema (HAE) is a rare autosomal dominant disease that commonly manifests with episodes of cutaneous or submucosal angioedema and intense abdominal pain. The condition usually presents due to a...

  18. Hereditary Angioedema: Report of Three Cases and Approach to Diagnosis and Management

    Sadiye Kuş

    2009-06-01

    Full Text Available Hereditary angioedema (HAE is a distinctive form of recurrent angioedema with life threatening consequences. Type I is defined with quantitative C1 esterase inhibitor (C1 INH deficiency, type II with functional C1 INH deficency and type III with normal quantity and function of C1 INH respectively. Here in, We present three cases with HAE and discuss diagnostic and therapeutic issues.

  19. Management of upper airway edema caused by hereditary angioedema

    Farkas Henriette

    2010-07-01

    Full Text Available Abstract Hereditary angioedema is a rare disorder with a genetic background involving mutations in the genes encoding C1-INH and of factor XII. Its etiology is unknown in a proportion of cases. Recurrent edema formation may involve the subcutis and the submucosa - the latter can produce obstruction in the upper airways and thereby lead to life-threatening asphyxia. This is the reason for the high, 30-to 50-per-cent mortality of undiagnosed or improperly managed cases. Airway obstruction can be prevented through early diagnosis, meaningful patient information, timely recognition of initial symptoms, state-of-the-art emergency therapy, and close monitoring of the patient. Prophylaxis can substantially mitigate the risk of upper airway edema and also improve the patients' quality of life. Notwithstanding the foregoing, any form of upper airway edema should be regarded as a potentially life-threatening condition. None of the currently available prophylactic modalities is capable of preventing UAE with absolute certainty.

  20. Prophylaxis in hereditary angioedema (HAE) with C1 inhibitor deficiency.

    Greve, Jens; Strassen, Ulrich; Gorczyza, Marina; Dominas, Nina; Frahm, Uta-Marie; Mühlberg, Heike; Wiednig, Michaela; Zampeli, Vasiliki; Magerl, Markus

    2016-03-01

    Hereditary angioedema (HAE) is a rare congenital disorder characterized by recurrent episodes of subcutaneous or submucosal edema. Laryngeal manifestations can be life-threatening. In the majority of cases, the disease can be adequately treated with an on-demand approach - in some cases, however, short- or long-term prophylaxis is indicated. Attenuated androgens used to be the drugs of choice, but they are associated with considerable side effects and no longer commercially available in the German-speaking countries of the EU. They are currently being replaced by more effective and more tolerable agents such C1-inhibitors, the kallikrein inhibitor ecallantide, and the B2 receptor antagonist icatibant, which have recently obtained market authorization. These new drugs have had a major impact, especially on the indications and procedures for long-term prophylaxis. According to the most recent international consensus papers and our own experience, self-administered C1-inhibitors are now the first option for long-term prophylactic therapy. The decision for prophylaxis should no longer be based on single parameters such as the frequency of attacks but on adequate overall disease control including quality of life. More drugs are currently being developed, which may lead to further changes in the treatment algorithms of HAE. PMID:26972189

  1. Hereditary Angioedema Attacks: Local Swelling at Multiple Sites.

    Hofman, Zonne L M; Relan, Anurag; Hack, C Erik

    2016-02-01

    Hereditary angioedema (HAE) patients experience recurrent local swelling in various parts of the body including painful swelling of the intestine and life-threatening laryngeal oedema. Most HAE literature is about attacks located in one anatomical site, though it is mentioned that HAE attacks may also involve multiple anatomical sites simultaneously. A detailed description of such multi-location attacks is currently lacking. This study investigated the occurrence, severity and clinical course of HAE attacks with multiple anatomical locations. HAE patients included in a clinical database of recombinant human C1-inhibitor (rhC1INH) studies were evaluated. Visual analog scale scores filled out by the patients for various symptoms at various locations and investigator symptoms scores during the attack were analysed. Data of 219 eligible attacks in 119 patients was analysed. Thirty-three patients (28%) had symptoms at multiple locations in anatomically unrelated regions at the same time during their first attack. Up to five simultaneously affected locations were reported. The observation that severe HAE attacks often affect multiple sites in the body suggests that HAE symptoms result from a systemic rather than from a local process as is currently believed. PMID:25527240

  2. [Treatment of drugs-associated non-hereditary angioedema mediated by bradykinin].

    Muller, Yannick; Harr, Thomas

    2016-01-13

    Angioedema is a deep intradermal or sub-cutaneous edema, which can be mediated by histamine, bradykinin or mixture of both components. The aims of this review are to describe the clinical approach and diagnosis of non-hereditary bradykinin-mediated angioedema induced by drugs such as: angiotensin-converting inhibitor, sartan, gliptins, rapamycin or some thrombolytic reagents and renin inhibitors. Furthermore, we will discuss the drug management of these angioedema, which is mainly based on C1 inhibitor concentrate or icatibant administration. PMID:26946694

  3. The therapeutic potential of a kallikrein inhibitor for treating hereditary angioedema.

    Levy, Jerrold H; O'Donnell, Penrose S

    2006-09-01

    Hereditary angioedema (HAE) manifests as intermittent, painful attacks of submucosal oedema affecting the larynx, gastrointestinal tract or limbs. Currently, acute treatment is available in Europe but not USA, and requires intravenous administration of a pooled blood product. HAE is most likely caused by dysinhibition of the contact cascade, resulting in overproduction of bradykinin. DX-88 (ecallantide, Dyax Corp.) is a highly specific recombinant plasma kallikrein inhibitor that halts the production of bradykinin and can be dosed subcutaneously. In a placebo-controlled Phase II trial in patients with HAE, DX-88 resulted in significant improvement in symptoms compared with placebo. A Phase III trial is ongoing. This review explains the pathophysiology of HAE and the mechanism by which DX-88, a non-intravenous, nonplasma-derived therapy, might improve the disease, and discusses the clinical course of HAE and available treatments. Finally, it explores the potential value and efficacy of DX-88 in treating HAE. PMID:16916274

  4. Current and emerging management options for hereditary angioedema in the US.

    Epstein, Tolly G; Bernstein, Jonathan A

    2008-01-01

    Hereditary angioedema (HAE) is a rare disorder characterized by recurrent attacks of swelling that may involve multiple anatomical locations. In the majority of patients, it is caused by a functional or quantitative defect in the C1 inhibitor (C1-INH), which is an important regulator of the complement, fibrinolytic, kallikrein-kinin and coagulation systems. Standard treatments used for other types of angioedema are ineffective for HAE. Traditional therapies for HAE, including fresh frozen plasma, epsilon-aminocaproic acid and danazol, may be well tolerated and effective in some patients; however, there are limitations both in their safety and efficacy. Several novel therapies have completed phase III trials in the US, including: (i) plasma-derived C1-INH replacement therapies (Berinert P and Cinryze); (ii) a recombinant C1-INH replacement therapy (conestat alfa; Rhucin); (iii) a kallikrein inhibitor (ecallantide [DX-88]); and (iv) a bradykinin-2-receptor antagonist (icatibant). Both Berinert P and Cinryze are reported to have excellent efficacy and safety data from phase III trials. Currently, only Cinryze has been approved for prophylactic use in the US. US FDA approval for other novel agents to treat HAE and for the use of Cinryze in the treatment of acute attacks is pending. PMID:19093699

  5. Diagnosis and treatment of hereditary angioedema with normal C1 inhibitor

    Bork Konrad

    2010-07-01

    Full Text Available Abstract Until recently it was assumed that hereditary angioedema is a disease that results exclusively from a genetic deficiency of the C1 inhibitor. In 2000, families with hereditary angioedema, normal C1 inhibitor activity and protein in plasma were described. Since then numerous patients and families with that condition have been reported. Most of the patients by far were women. In many of the affected women, oral contraceptives, hormone replacement therapy containing estrogens, and pregnancies triggered the clinical symptoms. Recently, in some families mutations in the coagulation factor XII (Hageman factor gene were detected in the affected persons.

  6. Urticaria and angioedema

    Kanani Amin

    2011-11-01

    Full Text Available Abstract Urticaria (hives is a common disorder that often presents with angioedema (swelling that occurs beneath the skin. It is generally classified as acute, chronic or physical. Second-generation, non-sedating H1-receptor antihistamines represent the mainstay of therapy for both acute and chronic urticaria. Angioedema can occur in the absence of urticaria, with angiotensin-converting enzyme (ACE inhibitor-induced angioedema and idiopathic angioedema being the more common causes. Rarer causes are hereditary angioedema (HAE or acquired angioedema (AAE. Although the angioedema associated with these disorders is often self-limited, laryngeal involvement can lead to fatal asphyxiation in some cases. The management of HAE and AAE involves both prophylactic strategies to prevent attacks of angioedema (i.e., trigger avoidance, attenuated androgens, tranexamic acid, and plasma-derived C1 inhibitor replacement therapy as well as pharmacological interventions for the treatment of acute attacks (i.e., C1 inhibitor replacement therapy, ecallantide and icatibant. In this article, the authors review the causes, diagnosis and management of urticaria (with or without angioedema as well as the work-up and management of isolated angioedema, which vary considerably from that of angioedema that occurs in the presence of urticaria.

  7. Angioedema hereditario: Guía de tratamiento Hereditary angioedema: A therapeutic guide

    Alejandro Malbrán

    2012-04-01

    Full Text Available El angioedema hereditario (HAE es una enfermedad rara, autosómica dominante, caracterizada por episodios que comprometen la piel, el tracto gastrointestinal y la laringe. Tiene una mortalidad histórica por asfixia del 15 al 50%. Es producida por la deficiencia funcional del C1 inhibidor. La identificación de la bradiquinina como mediador principal ha estimulado el desarrollo de nuevos medicamentos para tratar la enfermedad. El tratamiento del HAE se establece en consensos internacionales. El desarrollo de guías para el tratamiento de la enfermedad permite ordenar el uso de procedimientos diagnósticos y drogas. Describimos aquí algunas características farmacológicas de los medicamentos utilizados en el tratamiento del HAE en la Argentina: el concentrado plasmático de C1 inhibidor, el antagonista de la bradiquinina, icatibant, el andrógeno atenuado danazol y los agentes anti-fibrinolíticos ácidos épsilon aminocaproico (EACA y tranexámico. Asimismo, se describe su forma de uso y del control de los eventos adversos más frecuentes, así como las recomendaciones del último consenso internacional, aplicables para conformar una primera guía de tratamiento del HAE en la Argentina.Hereditary angioedema (HAE is a rare autosomal dominant disease, characterized by episodes of edema involving the skin, gastrointestinal tract and larynx. HAE has a historical asphyxia mortality of 15% to 50%. It is the consequence of functional C1 inhibitor deficiency. The identification of bradykinin as the principal mediator of the disease has lead to the development of new drugs for its treatment. HAE management and treatment are agreed by international consensus decision. A therapeutic guide for the treatment of the disease is important to improve diagnosis and treatment. We here describe the pharmacology of drugs available for the treatment of HAE in Argentina: plasma derived C1 Inhibitor, the bradykinin antagonist: icatibant, the attenuated androgen

  8. The role of ficolins and MASPs in hereditary angioedema due to C1-inhibitor deficiency

    Csuka, Dorottya; Munthe-Fog, Lea; Skjoedt, Mikkel-Ole; Kocsis, Andrea; Zotter, Zsuzsanna; Gál, Péter; Varga, Lilian; Farkas, Henriette; Füst, George; Garred, Peter

    Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) causes disturbances in the complement system. However, the influence of HAE-C1-INH on the lectin pathway of complement is unresolved. Thus, we studied the main initiator molecules, enzymes and regulators in the lectin pathway in...

  9. Mutational spectrum and phenotypes in Danish families with hereditary angioedema because of C1 inhibitor deficiency

    Bygum, A; Fagerberg, C R; Ponard, D; Monnier, N; Lunardi, J; Drouet, C

    2011-01-01

    Hereditary angioedema (HAE), type I and II, is an autosomal dominant disease with deficiency of functional C1 inhibitor protein causing episodic swellings of skin, mucosa and viscera. HAE is a genetically heterogeneous disease with more than 200 different mutations in the SERPING1 gene. A genotype...

  10. Depressed activation of the lectin pathway of complement in hereditary angioedema

    Varga, L; Széplaki, G; Laki, J; Kocsis, A; Kristóf, K; Gál, P; Bajtay, Z; Wieslander, J; Daha, M R; Garred, P; Madsen, H O; Füst, G; Farkas, H

    2008-01-01

    ) in three complement activation pathways. Functional activity of the CP, LP and AP were measured in the sera of 68 adult patients with hereditary angioedema (HAE) and 64 healthy controls. In addition, the level of C1q, MBL, MBL-associated serine protease-2 (MASP-2), C4-, C3- and C1INH was measured by...

  11. Presence of C1-Inhibitor Polymers in a Subset of Patients Suffering from Hereditary Angioedema

    Elenius Madsen, Daniel; Hansen, Søren; Gram, Jørgen Brodersen; Bygum, Anette; Drouet, Christian; Sidelmann, Johannes Jakobsen

    2014-01-01

    Hereditary angioedema (HAE) is a potentially life-threatening disease caused by mutations in the gene encoding the serine protease inhibitor (serpin) C1 inhibitor (C1-inh). The mutations cause decreased functional plasma levels of C1-inh, which triggers unpredictable recurrent edema attacks...

  12. Urticaria and Prodromal Symptoms Including Erythema Marginatum in Danish Patients with Hereditary Angioedema

    Rasmussen, Eva R; Valente de Freitas, Priscila; Bygum, Anette

    2015-01-01

    Erythema marginatum is a characteristic skin rash seen in patients with hereditary angioedema (HAE); however, it can be confused with urticaria, leading to delay in correct diagnosis. The aim of this study was to clarify how often erythema marginatum is misinterpreted as urticaria, potentially...

  13. Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III.

    Cichon, Sven; Martin, Ludovic; Hennies, Hans Christian; Müller, Felicitas; Van Driessche, Karen; Karpushova, Anna; Stevens, Wim; Colombo, Roberto; Renné, Thomas; Drouet, Christian; Bork, Konrad; Nöthen, Markus M

    2006-12-01

    Hereditary angioedema (HAE) is characterized clinically by recurrent acute skin swelling, abdominal pain, and potentially life-threatening laryngeal edema. Three forms of HAE have been described. The classic forms, HAE types I and II, occur as a consequence of mutations in the C1-inhibitor gene. In contrast to HAE types I and II, HAE type III has been observed exclusively in women, where it appears to be correlated with conditions of high estrogen levels--for example, pregnancy or the use of oral contraceptives. A recent report proposed two missense mutations (c.1032C-->A and c.1032C-->G) in F12, the gene encoding human coagulation factor XII (FXII, or Hageman factor) as a possible cause of HAE type III. Here, we report the occurrence of the c.1032C-->A (p.Thr328Lys) mutation in an HAE type III-affected family of French origin. Investigation of the F12 gene in a large German family did not reveal a coding mutation. Haplotype analysis with use of microsatellite markers is compatible with locus heterogeneity in HAE type III. To shed more light on the pathogenic relevance of the HAE type III-associated p.Thr328Lys mutation, we compared FXII activity and plasma levels in patients carrying the mutation with that of healthy control individuals. Our data strongly suggest that p.Thr328Lys is a gain-of-function mutation that markedly increases FXII amidolytic activity but that does not alter FXII plasma levels. We conclude that enhanced FXII enzymatic plasma activity in female mutation carriers leads to enhanced kinin production, which results in angioedema. Transcription of F12 is positively regulated by estrogens, which may explain why only women are affected with HAE type III. The results of our study represent an important step toward an understanding of the molecular processes involved in HAE type III and provide diagnostic and possibly new therapeutic opportunities. PMID:17186468

  14. Treatment of type I and II hereditary angioedema with Rhucin, a recombinant human C1 inhibitor.

    Varga, Lilian; Farkas, Henriette

    2008-11-01

    Hereditary and acquired angioedema are of outstanding clinical importance, as edematous attacks associated with these conditions can thrust afflicted patients into mortal danger. Currently, C1 inhibitor concentrate - a human blood product - is available as a replacement therapy. In view of the limited number of donors, as well as the risk of transmission of blood-borne infections, it is a reasonable expectation to develop a therapeutic alternative based on recombinant technology, which would eliminate all these shortcomings. Pharming (Leiden, The Netherlands) has developed Rhucin, a recombinant human C1 inhibitor, as a proprietary product, which is currently being evaluated in Phase III clinical trials. Ongoing studies conducted within the framework of the development program are almost complete and their interim findings are reassuring. This should facilitate successful regulatory approval in the near future, which is indispensable in order to make Rhucin available for patients with hereditary angioedema or other disorders amenable to C1 inhibitor replacement. PMID:20477114

  15. Hereditary angioderma: an uncommon cause of acute abdomen. Abdominal computed tomography and ultrasound findings; Angioedema hereditario: una causa infrecuente de abdomen agudo. Hallazgos en la TC e ecografia abdominal

    Cruz, R.A. de la; Oliver, J. M.; Bueno, A.; Albillos, J. C. [Fundacion Hospital Alcorcon. Madrid (Spain)

    2002-07-01

    We present an uncommon case of acute abdomen in a patient with hereditary angioderma. The ultrasound and CT findings described may suggest this diagnosis, thus avoiding useless surgical interventions in patients in whom the disease has not been previously diagnosed. (Author) 19 refs.

  16. Successful C1 inhibitor short-term prophylaxis during redo mitral valve replacement in a patient with hereditary angioedema

    Coleman Suzanne

    2010-10-01

    Full Text Available Abstract Hereditary angioedema is characterized by sudden episodes of nonpitting edema that cause discomfort and pain. Typically the extremities, genitalia, trunk, gastrointestinal tract, face, and larynx are affected by attacks of swelling. Laryngeal swelling carries significant risk for asphyxiation. The disease results from mutations in the C1 esterase inhibitor gene that cause C1 esterase inhibitor deficiency. Attacks of hereditary angioedema result from contact, complement, and fibrinolytic plasma cascade activation, where C1 esterase inhibitor irreversibly binds substrates. Patients with hereditary angioedema cannot replenish C1 esterase inhibitor levels on pace with its binding. When C1 esterase inhibitor is depleted in these patients, vasoactive plasma cascade products cause swelling attacks. Trauma is a known trigger for hereditary angioedema attacks, and patients have been denied surgical procedures because of this risk. However, uncomplicated surgeries have been reported. Appropriate prophylaxis can reduce peri-operative morbidity in these patients, despite proteolytic cascade and complement activation during surgical trauma. We report a case of successful short-term prophylaxis with C1 esterase inhibitor in a 51-year-old man with hereditary angioedema who underwent redo mitral valve reconstructive surgery.

  17. Hereditary angioedema: Historical aspects, classification, pathophysiology, clinical presentation, and laboratory diagnosis.

    Khan, David A

    2011-01-01

    Hereditary angioedema (HAE) is a rare disorder first described in 1888 by Sir William Osler. Since then, our understanding of this condition has increased tremendously. This article reviews the historical aspects, classification, pathophysiology, clinical presentation, and laboratory diagnosis of HAE. A review was performed of historical and current literature of HAE. HAE I and II are related to insufficient production of C1-esterase inhibitor (C1-INH) or production of a dysfunctional C1-INH protein, respectively. HAE III is not related to C1-INH deficiency and the pathogenesis is unknown. Bradykinin appears to be the main mediator responsible for angioedema in patients with C1-INH deficiencies. Angioedema of the extremities, face, and upper airway along with gastrointestinal angioedema are the most common clinical features in HAE. The laboratory tests that are most commonly used in the diagnosis of HAE include C4, C1-INH concentration, and C1-INH function. Advances in our understanding of the pathogenesis of HAE have led to several advances in the therapy of this disease. Despite our more thorough understanding of the genetics and pathophysiology of HAE, many questions remain unanswered. PMID:21262092

  18. Treatment of Hereditary Angioedema: items that need to be addressed in practice parameter

    Dagen Callie

    2010-05-01

    Full Text Available Abstract Background Hereditary Angioedema (HAE is a rare, autosomal dominant (AD disorder caused by a C1 esterase inhibitor (C1-inh deficiency or qualitative defect. Treatment of HAE in many parts of the world fall short and certain items need to be addressed in future guidelines. Objective To identify those individuals who should be on long-term prophylaxis for HAE. Additionally, to determine if prodromal symptoms are sensitive and specific enough to start treatment with C-1 INH and possibly other newly approved therapies. Also, to discuss who is appropriate to self-administer medications at home and to discuss training of such patients. Methods A literature review (PubMed and Google was performed and articles published in peer-reviewed journals, which addressed HAE prophylaxis, current HAE treatments, prodromal symptoms of HAE and self-administration of injected home medications were selected, reviewed and summarized. Results Individuals whom have a significant decrease in QOL or have frequent or severe attacks and who fail or are intolerant to androgens should be considered for long-term prophylaxis with C1INH. Prodromal symptoms are sensitive, but non-specific, and precede acute HAE attacks in the majority of patients. Although the treatment of prodromal symptoms could lead to occasional overtreatment, it could be a viable option for those patients able to adequately predict their attacks. Finally, self-administration, has been shown to be feasible, safe and effective for patients who require IV therapy for multiple other diseases to include, but not limited to, hemophilia. Conclusions Prophylactic therapy, treatment at the time of prodromal symptoms and self-administration at home all should allow a reduction in morbidity and mortality associated with HAE.

  19. On demand treatment and home therapy of hereditary angioedema in Germany - the Frankfurt experience

    Aygören-Pürsün Emel

    2010-07-01

    Full Text Available Abstract Background Manifestation of acute edema in hereditary angioedema (HAE is characterized by interindividual and intraindividual variability in symptom expression over time. Flexible therapy options are needed. Methods We describe and report on the outcomes of the highly individualized approach to HAE therapy practiced at our HAE center in Frankfurt (Germany. Results The HAE center at the Frankfurt University Hospital currently treats 450 adults with HAE or AAE and 107 pediatric HAE patients with highly individualized therapeutic approaches. 73.9% of the adult patients treat HAE attacks by on-demand therapy with pasteurized pd C1-INH concentrate, 9.8% use additional prophylaxis with attenuated androgens, 1% of the total patient population in Frankfurt has been treated with Icatibant up to now. In addition adult and selected pediatric patients with a high frequency of severe attacks are instructed to apply individual replacement therapy (IRT with pasteurized pd C1-INH concentrate. Improvement on Quality of Life items was shown for these patients compared to previous long-term danazol prophylaxis. Home treatment of HAE patients was developed in the Frankfurt HAE center in line with experiences in hemophilia therapy and has so far been implemented over a period of 28 years. At present 248 (55% of the adult patients and 26 (24% of the pediatric patients are practicing home treatment either as on demand or IRT treatment. Conclusions In conclusion, the individualized home therapies provided by our HAE center, aim to limit the disruption to normal daily activities that occurs for many HAE patients. Furthermore, we seek to optimize the economic burden of the disease while offering a maximum quality of life to our patients.

  20. Hereditary angioedema presenting as irritable bowel syndrome: a case of early closure

    Karim M. Benrajab

    2015-10-01

    Full Text Available Abdominal pain is one of the most common reasons for outpatient and emergency department visits. We present one such case of early closure in a 32-year-old male with recurrent abdominal pain who was diagnosed with irritable bowel syndrome (IBS. Family history was suspicious for hereditary angioedema (HAE. The HAE workup came back positive, and the patient was started on prophylactic therapy, which led to an improvement in symptoms and quality of life. The purpose of this case is to create awareness among physicians to test for HAE in patients diagnosed with IBS who, based on their history or physical examination, have clinical suspicion for HAE.

  1. Hereditary angioedema presenting as irritable bowel syndrome: a case of early closure

    Benrajab, Karim M.; Singh, Gurkeerat; Obah, Eugene

    2015-01-01

    Abdominal pain is one of the most common reasons for outpatient and emergency department visits. We present one such case of early closure in a 32-year-old male with recurrent abdominal pain who was diagnosed with irritable bowel syndrome (IBS). Family history was suspicious for hereditary angioedema (HAE). The HAE workup came back positive, and the patient was started on prophylactic therapy, which led to an improvement in symptoms and quality of life. The purpose of this case is to create awareness among physicians to test for HAE in patients diagnosed with IBS who, based on their history or physical examination, have clinical suspicion for HAE. PMID:26486119

  2. Hereditary Angioedema and Gastrointestinal Complications: An Extensive Review of the Literature

    Patel, Napoleon; Suarez, Lisbet D.; Kapur, Sakshi; Bielory, Leonard

    2015-01-01

    Hereditary Angioedema (HAE) is a rare autosomal dominant (AD) disease characterized by deficient (type 1) or nonfunctional (type 2) C1 inhibitor protein. The disorder is associated with episodes of angioedema of the face, larynx, lips, abdomen, or extremities. The angioedema is caused by the activation of the kallikrein-kinin system that leads to the release of vasoactive peptides, followed by edema, which in severe cases can be life threatening. The disease is usually not diagnosed until late adolescence and patients tend to have frequent episodes that can be severely impairing and have a high incidence of morbidity. Gastrointestinal involvement represents up to 80% of clinical presentations that are commonly confused with other gastrointestinal disorders such as appendicitis, cholecystitis, pancreatitis, and ischemic bower. We present a case of an HAE attack presenting as colonic intussusception managed conservatively with a C1 esterase inhibitor. Very few cases have been reported in the literature of HAE presentation in this manner, and there are no reports of any nonsurgical management of these cases. PMID:26339513

  3. Ecallantide is a novel treatment for attacks of hereditary angioedema due to C1 inhibitor deficiency

    Farkas H

    2011-05-01

    Full Text Available Henriette Farkas, Lilian Varga3rd Department of Internal Medicine, Semmelweis University, Budapest, HungaryAbstract: Hereditary angioedema (HAE resulting from the deficiency of the C1 inhibitor protein is a rare disease, characterized by paroxysms of edema formation in the subcutis and in the submucosa. Edema can cause obstruction of the upper airway, which may lead to suffocation. Prompt elimination of edema is necessary to save patients from this life-threatening condition. Essentially, these edematous attacks are related to the activation of the kinin-kallikrein system and the consequent release of bradykinin. Ecallantide (known as DX-88 previously, a potent and specific inhibitor of plasma kallikrein is an innovative medicinal product. This is the only agent approved recently by the FDA for all localizations of edematous HAE attacks. Its advantages include no risk of viral contamination, high selectivity, very rapid onset of action, good tolerability, and straightforward subcutaneous administration. Owing to the risk of anaphylaxis, ecallantide should be administered by a health care professional. A postmarketing survey to improve risk-assessment and risk-minimization has been launched. The results of these studies may lead to the approval of ecallantide for self-administration.Keywords: hereditary angioedema, C1-inhibitor deficiency, treatment, bradykinin, kallikrein inhibitor, subcutaneous administration

  4. The establishment and utility of Sweha-Reg: a Swedish population-based registry to understand hereditary angioedema

    Werner Sonja

    2007-11-01

    Full Text Available Abstract Background The importance of acquiring comprehensive epidemiological and clinical data on hereditary angioedema has increasingly caught the attention of physicians and scientists around the world. The development of networks and creation of comprehensive policies to improve care of people suffering from rare diseases, such as hereditary angioedema, is a stated top priority of the European Union. Hereditary angioedema is a rare disease, that it may be life-threatening. Although the exact prevalence is unknown, current estimates suggest that it is 1/10,000–1/150,000 individuals. The low prevalence requires combined efforts to gain accurate epidemiological data on the disease and so give us tools to reduce morbidity and mortality, and improve quality of life of sufferers. Methods Sweha-Reg is a population-based registry of hereditary angioedema in Sweden with the objectives of providing epidemiological data, and so creates a framework for the study of this disease. The registry contains individual-based data on diagnoses, treatments and outcomes. Conclusion The present manuscript seeks to raise awareness of the existence of Sweha-Reg to stimulate the international collaboration of registries. A synthesis of data from similar registries across several countries is required to approach an inclusive course understanding of HAE.

  5. Acute urticaria and angioedema caused by horse-chestnut (aesculus hippocastanum) ingestion: a case report

    Akinci, Emine; OĞUZTÜRK, Oğuzhan; Coşkun, Figen

    2012-01-01

    Acute urticaria and angioedema, which can develop due to various causes, are common life threatening condition seen in emergency departments (EDs). The literature includes reports of angioedema cases developing after contacting various plants and seeds. We present the case of a 47-year-old male patient who developed acute urticaria and angioedema after eating horse-chestnut (aesculus hippocastanum). The patient presented to the ED with redness and irritation spread around the body and swellin...

  6. Hereditary Angioedema due to C1 Inhibitor Deficiency: C1-INH Replacement Therapy

    Mauro Cancian

    2014-04-01

    Full Text Available Hereditary angioedema (HAE is a rare condition affecting about 1 in 50.000 individuals and caused by a mutation in the gene encoding the C1-esterase inhibitor (C1-INH, which is involved in the control of complement, clotting, fibrinolytic and kinin pathways. HAE is characterized by plasma outflow from blood vessels, leading to fluid collecting (edema in the deep tissue layers of the face, larynx, abdomen, and extremities. Three different types of HAE have been identified: in type I the mutation leads to the lack of production of C1-INH, in type II the mutation leads to the production of dysfunctional C1-INH, while type III is extremely rare and still not fully understood. Therapeutic approaches for HAE include on-demand treatments to stop angioedema attacks and prophylactic treatment to prevent attacks both by pre-procedural (short-term and routine (long-term prophylaxis. Aim of the present review is to present an overview of C1-INH replacement therapy with the plasma-derived concentrate of C1-INH Berinert® (CSL Behring GmbH in the treatment of type I and II HAE.http://dx.doi.org/10.7175/rhc.v5i2.913

  7. The hereditary angioedema burden of illness study in Europe (HAE-BOIS- Europe)

    Bygum, Anette; Aygören-Pürsün, Emel; Caballero, Teresa;

    2012-01-01

    ABSTRACT: BACKGROUND: Hereditary angioedema (HAE) is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation......-BOIS-Europe), the development and methodology of which is described here, is to better understand the management and impact of HAE from the patient perspective in Europe. METHODS: This is a cross-sectional study being conducted in Denmark, Germany and Spain. The study is open to patients ages 12 and older with a...... collect detailed descriptive data and patient testimonials on the impact of HAE on patients' health-related quality of life. CONCLUSION: The present manuscript describes the development and plans for implementing a multi-country European study with the aim of characterizing the humanistic and economic...

  8. Coexistence of hereditary angioedema in a case of familial Mediterranean fever with partial response to colchicine

    Bahceci, Semiha Erdem; Genel, Ferah; Gulez, Nesrin

    2015-01-01

    Hereditary angioedema (HAE) is a very rare and potentially life-threatening genetic disease characterised by episodes of edema in various parts of the body, including the extremities, face, and airway. The disease is usually associated with attacks of abdominal pain. On the other hand, familial Mediterranean fever (FMF) is an inherited condition characterised by recurrent episodes of painful inflammation in the abdomen, chest, or joints. In this report, we present a child with FMF and undiagnosed HAE, which made him a partial responder to colchicine treatment. Consequently, HAE must be considered in differential diagnosis of cases in which a partial response is obtained from FMF treatment, particularly in countries where FMF is frequently encountered, because early diagnosis of HAE can facilitate prevention of life-threatening complications, such as upper airway obstruction. To our knowledge, our patient is the first patient reported in the literature with the diagnosis of HAE and FMF together. PMID:26155193

  9. Hereditary angioedema: special consideration in children, women of childbearing age, and the elderly.

    Kuhlen, James L; Banerji, Aleena

    2015-01-01

    This review on hereditary angioedema (HAE) focused on special topics regarding HAE in children, women of childbearing age, and the elderly. HAE is a rare autosomal dominant bradykinin-mediated disorder characterized by recurrent attacks of subcutaneous or submucosal swelling that usually affects the face, upper airway, extremities, gastrointestinal tract, or genitalia. These recurrent attacks cause significant morbidity and can be life threatening, especially when the swelling affects the airway. Our objective was to summarize the published data available on the disease epidemiology, pathophysiology, clinical presentation, on demand and prophylactic therapy, and focus on management considerations for these special patient populations. Unique aspects of HAE in women with regard to contraception, hormone replacement therapy, pregnancy, lactation, and menopause were also reviewed. PMID:26534748

  10. Urticaria and Prodromal Symptoms Including Erythema Marginatum in Danish Patients with Hereditary Angioedema.

    Rasmussen, Eva R; de Freitas, Priscila Valente; Bygum, Anette

    2016-03-01

    Erythema marginatum is a characteristic skin rash seen in patients with hereditary angioedema (HAE); however, it can be confused with urticaria, leading to delay in correct diagnosis. The aim of this study was to clarify how often erythema marginatum is misinterpreted as urticaria, potentially leading physicians to refrain from testing for HAE. Few studies have been published on urticaria and prodromal symptoms in HAE, thus the incidence of these parameters were also investigated. A total of 87 patients affiliated to the national HAE Centre were included. Retrospective and prospective data on skin eruptions and prodromal symptoms were collected. Fifty-six percent of 87 patients had a positive history of erythema marginatum. Half of the patients had experienced erythema marginatum being misinterpreted as urticaria. The most prevalent other prodromal symptoms were other skin symptoms, malaise, psychological changes, fatigue and gastrointestinal symptoms. HAE patients with erythema marginatum have a longer diagnostic delay, presumably caused by misinterpretation of the rash as urticaria. PMID:26336842

  11. HAE update: special considerations in the female patient with hereditary angioedema.

    Geng, Bob; Riedl, Marc A

    2013-01-01

    This review on hereditary angioedema (HAE) focuses on special topics regarding HAE in female patients. HAE is a bradykinin-mediated disorder, and the role of hormonal regulation of disease expression will be discussed focusing on the effect of estrogen on disease mechanism. The impact of exogenous estrogen on symptom exacerbation leads to special consideration regarding choice of contraceptives and safety of hormone replacement therapy. The effects of pregnancy and childbirth will be examined on the course of disease control. Unique considerations regarding therapeutic management for female HAE patients will be addressed, including the role of C1 inhibitor (C1-INH), ecallantide, and icatibant. Finally, this review will provide an overview of the more recently characterized HAE with normal C1-INH (HAE type III) that predominantly affects women and is in some cases associated with factor XII gene mutations. PMID:23406930

  12. Obstetrical Complications and Outcome in Two Families with Hereditary Angioedema due to Mutation in the F12 Gene.

    Picone, Olivier; Donnadieu, Anne-Claire; Brivet, François G; Boyer-Neumann, Catherine; Frémeaux-Bacchi, Véronique; Frydman, René

    2010-01-01

    Backgroud. Hereditary angioedema (HAE) is characterized by recurrent swelling of the skin, the abdomen (causing severe acute pain), and the airways. A recently discovered type caused by mutations in the factor XII gene (designated as HAE type III) occurs mainly in women. Estrogens may play an important role, but few obstetrical complications have been reported. Case. We report the symptoms and obstetrical complications of women in two families with HAE attributable to the p. Thr328Lys mutation in the F12 gene. Clinical manifestations included acute and severe maternal abdominal pain, with transient ascites, laryngeal edema, and fetal and neonatal deaths. Patients had normal C4 levels and a normal C1 inhibitor gene. Administration of C1-inhibitor concentration twice monthly decreased the attack rate in one mother, and its predelivery administration (1000 U) led to the delivery of healthy girls. Conclusions. Obstetricians and anesthesiologists should be aware of this rare cause of unexplained maternal ascites and in utero or fetal death associated with edema. PMID:20490261

  13. Canadian 2003 International Consensus Algorithm For the Diagnosis, Therapy, and Management of Hereditary Angioedema.

    Bowen, Tom; Cicardi, Marco; Farkas, Henriette; Bork, Konrad; Kreuz, Wolfhart; Zingale, Lorenza; Varga, Lilian; Martinez-Saguer, Inmaculada; Aygören-Pürsün, Emel; Binkley, Karen; Zuraw, Bruce; Davis, Alvin; Hebert, Jacques; Ritchie, Bruce; Burnham, Jeanne; Castaldo, Anthony; Menendez, Alejandra; Nagy, Istvan; Harmat, George; Bucher, Christoph; Lacuesta, Gina; Issekutz, Andrew; Warrington, Richard; Yang, William; Dean, John; Kanani, Amin; Stark, Donald; McCusker, Christine; Wagner, Eric; Rivard, Georges-Etienne; Leith, Eric; Tsai, Ellie; MacSween, Michael; Lyanga, John; Serushago, Bazir; Leznoff, Art; Waserman, Susan; de Serres, Jean

    2004-09-01

    C1 inhibitor deficiency (hereditary angioedema [HAE]) is a rare disorder for which there is a lack of consensus concerning diagnosis, therapy, and management, particularly in Canada. European initiatives have driven the approach to managing HAE with 3 C1-INH Deficiency Workshops held every 2 years in Hungary starting in 1999, with the third Workshop having recently been held in May 2003. The European Contact Board has established a European HAE Registry that will hopefully advance our knowledge of this disorder. The Canadian Hereditary Angioedema Society/Société d'Angioédème Héréditaire du Canada organized a Canadian International Consensus Conference held in Toronto, Ontario, Canada, on October 24 to 26, 2003, to foster consensus between major European and North American HAE treatment centers. Papers were presented by investigators from Europe and North America, and this consensus algorithm approach was discussed. There is a paucity of double-blind placebo-controlled trials in the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Enclosed is the consensus algorithm approach recommended for the diagnosis, therapy, and management of HAE and agreed to by the authors of this article. This document is only a consensus algorithm approach and requires validation. As such, participants agreed to make this a living 2003 algorithm (ie, a work in progress) and agreed to review its content at future international HAE meetings. The consensus, however, has strength in that it was arrived at by the meeting of patient-care providers along with patient group representatives and individual patients reviewing information available to date and reaching agreement on how to approach the diagnosis, therapy, and management of HAE circa 2003. Hopefully evidence to support approaches to the management of HAE will approach the level of meta-analysis of randomized controlled trials in the near future. PMID:15356569

  14. Enzymatic pathways in the pathogenesis of hereditary angioedema: the role of C1 inhibitor therapy.

    Kaplan, Allen P

    2010-11-01

    A functional abnormality of C1 inhibitor (C1INH) is present in types I and II hereditary angioedema (HAE), and normal C1INH may be rendered ineffective in the newly described type III HAE. C1INH inhibits factor XIIa, factor XII fragment (XIIf), kallikrein, and plasmin. Thus, in its absence, there is marked activation of the bradykinin-forming cascade resulting in severe angioedema. Factor XII may autoactivate on binding to endothelial cell surface gC1qR (receptor for the globular heads of C1q) thus initiating the cascade. Alternatively, stimuli that activate endothelial cells may liberate (or express at the cell surface) heat shock protein 90 or the enzyme prolylcarboxypeptidase, either of which can interact with the prekallikrein-high-molecular-weight kininogen complex to convert prekallikrein to kallikrein stoichiometrically. The kallikrein produced can cleave high-molecular-weight kininogen to produce bradykinin and also recruit factor XII by enzymatically activating it. Patients with type I or II HAE have mutant C1INH so that control of C1 activation is lost. Autoactivation of C1r in the absence of C1INH leads to C1s activation followed by C4 cleavage and depletion. An attack of swelling is accompanied by conversion of factor XIIa to factor XIIf and further enzymatic activation of C1r so that C4 levels drop further and C2 is depleted. New therapies for HAE focus on the bradykinin-forming cascade and include a kallikrein inhibitor and a bradykinin B-2 receptor antagonist in addition to administration of purified C1INH. PMID:20889195

  15. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III

    Björkqvist, Jenny; de Maat, Steven; Lewandrowski, Urs; Di Gennaro, Antonio; Oschatz, Chris; Schönig, Kai; Nöthen, Markus M.; Drouet, Christian; Braley, Hal; Nolte, Marc W.; Sickmann, Albert; Panousis, Con; Maas, Coen; Renné, Thomas

    2015-01-01

    Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12–/– mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes. PMID:26193639

  16. Genetic analysis of hereditary angioedema in a Brazilian family by targeted next generation sequencing.

    Veronez, Camila Lopes; da Silva, Elton Dias; Lima Teixeira, Patrícia Varela; Cagini, Nathália; Constantino-Silva, Rosemeire Navickas; Grumach, Anete Sevciovic; Mansour, Eli; Velloso, Lício A; Pesquero, João Bosco

    2016-04-01

    Hereditary angioedema (HAE) is accompanied by an overproduction of bradykinin (BK) as the primary mediator of swelling. Although many proteins may be involved in regulating the wide spectrum of HAE symptoms, most studies have only focused on C1-INH and FXII. For the first time, a next generation sequencing (NGS) method was applied to develop a robust, time- and cost-effective diagnostic and research tool to analyze selected genes related to HAE. The entire coding region and the exon-intron boundaries of 15 genes from 23 subjects of a Brazilian family, nine of whom were symptomatic, were analyzed by NGS. One new mutation found uniquely in the nine symptomatic patients, p.Ala457Pro in the SERPING1 gene, was estimated as likely to be pathogenic (PolyPhen-2 software analysis) and is the main candidate to be responsible for HAE in these patients. Alterations identified in a few asymptomatic individuals but also found in almost all symptomatic patients, such as p.Ile197Met (HMWK), p.Glu298Asp (NOS3) and p.Gly354Glu (B2R), may also be involved in modulating patient-specific symptoms. This NGS gene panel has proven to be a valuable tool for a quick and accurate molecular diagnosis of HAE and efficient to indicate modulators of HAE symptoms. PMID:26751894

  17. Erythema Marginatum as an Early Symptom of Hereditary Angioedema: Case Report of 2 Newborns.

    Martinez-Saguer, Inmaculada; Farkas, Henriette

    2016-02-01

    Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare genetic disease that causes recurrent swelling attacks that may affect various body tissues. Angioedematous attacks can be fatal in the case of upper airway edema and are often preceded by prodromal symptoms like erythema marginatum. Initial symptoms usually occur in the first decade of life. We report on manifestation of profound and recurrent erythema marginatum in 2 newborns. In both cases, prodromal symptoms could help determine the diagnosis of C1-INH-HAE such that, at a later time, angioedematous attacks could be treated promptly and effectively. Awareness of C1-INH-HAE is low among physicians and even lower among the general public. This report aims at raising the level of awareness and shows that initial symptoms of the potentially life-threatening condition can manifest in newborns and that erythema marginatum can even be present at birth. Recognition of early symptoms and timely diagnosis of the disease along with adequate education of the pediatrician and parents are a prerequisite for prompt and effective treatment of attacks and the successful management of the disease. PMID:26759410

  18. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III.

    Björkqvist, Jenny; de Maat, Steven; Lewandrowski, Urs; Di Gennaro, Antonio; Oschatz, Chris; Schönig, Kai; Nöthen, Markus M; Drouet, Christian; Braley, Hal; Nolte, Marc W; Sickmann, Albert; Panousis, Con; Maas, Coen; Renné, Thomas

    2015-08-01

    Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12-/- mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes. PMID:26193639

  19. Intestinal Angioedema Misdiagnosed as Recurrent Episodes of Gastroenteritis

    LoCascio, Edward J

    2010-09-01

    Full Text Available Emergency physicians (EP frequently encounter angioedema involving the lips and tongue. However, angioedema from Angiotensin Converting Enzyme inhibitors or hereditary angioedema (HAE can present with gastrointestinal symptoms due to bowel wall involvement. EPs should begin to consider this clinical entity as a potential cause for abdominal pain and associated gastrointestinal symptoms given the common use of medications that can precipitate angioedema. We report a case of a 34-year-old woman who presented with abdominal cramping, vomiting and diarrhea due to an acute exacerbation of HAE. [West J Emerg Med. 2010; 11(4:391-394.

  20. Hereditary angioedema. Long-term follow-up of 88 patients. Experience of the Argentine Allergy and Immunology Institute.

    Fabiani, J E; Avigliano, A; Dupont, J C; Fabiana, J E

    2000-01-01

    Since the detection of the first patient with hereditary angioedema (HA) in 1978, 88 new patients belonging to 16 families have been referred to our clinic. Eighty patients had Type I disease, 5 Type II, and 3 Type III (secondary). We describe the clinical onset, frequent complications, diagnostic tests of the complement system, and abnormalities of the coagulation pathway linked to complement activation. Particular attention was paid to family members who could present succedaneum symptoms. The results of danazole and other therapies and protective and preventive treatment for surgery also are discussed. PMID:11270087

  1. Novel Vasoregulatory Aspects of Hereditary Angioedema: the Role of Arginine Vasopressin, Adrenomedullin and Endothelin-1.

    Kajdácsi, Erika; Jani, Péter K; Csuka, Dorottya; Varga, Lilian; Prohászka, Zoltán; Farkas, Henriette; Cervenak, László

    2016-02-01

    The elevation of bradykinin (BK) level during attacks of hereditary angioedema due to C1-Inhibitor deficiency (C1-INH-HAE) is well known. We previously demonstrated that endothelin-1 (ET-1) level also increases during C1-INH-HAE attacks. Although BK and ET-1 are both potent vasoactive peptides, the vasoregulatory aspect of the pathomechanism of C1-INH-HAE has not yet been investigated. Hence we studied the levels of vasoactive peptides in controls and in C1-INH-HAE patients, as well as evaluated their changes during C1-INH-HAE attacks. The levels of arginine vasopressin (AVP), adrenomedullin (ADM) and ET-1 were measured in the plasma of 100 C1-INH-HAE patients in inter-attack periods and of 111 control subjects, using BRAHMS Kryptor technologies. In 18 of the 100 C1-INH-HAE patients, the levels of vasoactive peptides were compared in blood samples obtained during attacks, or in inter-attack periods. AVP, ADM and ET-1 levels were similar in inter-attack samples from C1-INH-HAE patients and in the samples of controls, although cardiovascular risk has an effect on the levels of vasoactive peptides in both groups. The levels of all three vasoactive peptides increased during C1-INH-HAE attacks. Moreover, the levels of ET-1 and ADM as well as their changes during attacks were significantly correlated. This study demonstrated that vascular regulation by vasoactive peptides is affected during C1-INH-HAE attacks. Our results suggest that the cooperation of several vasoactive peptides may be necessary to counterbalance the actions of excess BK, and to terminate the attacks. This may reveal a novel pathophysiological aspect of C1-INH-HAE. PMID:26873707

  2. New mutations in SERPING1 gene of Brazilian patients with hereditary angioedema.

    Cagini, Nathália; Veronez, C L; Constantino-Silva, R N; Buzolin, Márcia; Martin, Renan Paulo; Grumach, A S; Velloso, Lício Augusto; Mansour, Eli; Pesquero, João Bosco

    2016-04-01

    Hereditary Angioedema is an autosomal dominant inherited disease leading to oedema attacks with variable severity and localization predominantly caused by C1-INH deficit. More than 400 mutations have been already identified, however no genetic analysis of a Brazilian cohort of HAE patients with C1-INH deficiency has been published. Our aim was to perform genetic analysis of C1-INH gene (SERPING1) in Brazilian HAE patients. We screened the whole SERPING1 coding region from 30 subjects out of 16 unrelated families with confirmed diagnosis of HAE due to C1-INH deficiency. Clinical diagnosis was based on symptoms and quantitative and/or functional analysis of C1-INH. We identified fifteen different mutations among which eight were not previously described according to databases. We found five small deletions (c.97_115del19; c.553delG; c.776_782del7; c.1075_1089del15 and c.1353_1354delGA), producing frameshifts leading to premature stop codons; seven missense mutations (c.498C>A; c.550G>C; c.752T>C; c.889G>A; c.1376C>A; c.1396C>T; c.1431C>A); one nonsense mutation (c.1480C>T), and two intronic alterations (c.51+1G>T; c.51+2T>C). Despite the small number of participants in this study, our results show mutations not previously identified in SERPING1 gene. This study represents the first Brazilian HAE cohort evaluated for mutations and it introduces the possibility to perform genetic analysis in case of need for differential diagnosis. PMID:26812872

  3. The hereditary angioedema burden of illness study in Europe (HAE-BOIS-Europe: background and methodology

    Bygum Anette

    2012-04-01

    Full Text Available Abstract Background Hereditary angioedema (HAE is a rare but serious disease marked by swelling attacks in the extremities, face, trunk, airway, or abdominal areas that can be spontaneous or the result of trauma and other triggers. It can be life-threatening due to the risk of asphyxiation. While there have been major advancements in our understanding of the immunogenetics of HAE, there are significant gaps in the literature regarding understanding of the humanistic and economic impact of the disease, particularly in Europe. The purpose of the HAE Burden of Illness Study-Europe (HAE-BOIS-Europe, the development and methodology of which is described here, is to better understand the management and impact of HAE from the patient perspective in Europe. Methods/Design This is a cross-sectional study in which retrospective data were also collected being conducted in Denmark, Germany and Spain. The study is open to patients ages 12 and older with a diagnosis of HAE-I or HAE-II. Data collection includes: (i a survey on individuals’ health care resource use, direct and indirect medical costs, impact on work and school, treatment satisfaction, and emotional functioning (via the Hospital Anxiety and Depression Scale; and (ii one-on-one interviews to collect detailed descriptive data and patient testimonials on the impact of HAE on patients’ health-related quality of life. Discussion The present manuscript describes the development and plans for implementing a multi-country European study with the aim of characterizing the humanistic and economic burden of HAE from the patient perspective. This study will help raise awareness of HAE as a rare but debilitating condition with wide-ranging impacts.

  4. 86 The Efficacy and Safety of Human Plasma-derived C1-Inhibitor Concentrate Administered for the Treatment of Attacks in Pediatric Patients with Hereditary Angioedema Due to C1-Inhibitor Deficiency

    Farkas, Henriette; Csuka, Dorottya; Zotter, Zsuzsanna; Szabó, Erika; Kelemen, Zsuzsanna; Varga, Lilian; Fejes, János; Harmat, George

    2012-01-01

    Background Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a life-threatening, rare disease characterized by recurrent edematous attacks. In 50% of cases, the initial onset of symptoms occurs between 5 and 11 years of age. There are limited data on the emergency treatment of acute episodes in pediatric patients. Our aim was to analyze the efficacy and safety of human plasma-derived C1-INH concentrate in our pediatric patient population with HAE-C1-INH. Methods 50 pediatri...

  5. Anaphylactoid reactions and angioedema during alteplase treatment of acute ischemic stroke

    Hill, M D; Barber, P.A.; Takahashi, J.; Demchuk, A.M.; Feasby, T E; Buchan, A M

    2000-01-01

    Among 105 patients given recombinant tissue plasminogen activator (rt-PA, alteplase) intravenously for acute stroke, 2 (1.9%) had lingual angioedema, which progressed to a fatal anaphylactoid reaction in 1. The authors review the 2 cases and possible mechanisms responsible. They warn that patients who are taking an angiotensin-converting-enzyme inhibitor may be at increased risk for angioedema with concomitant alteplase therapy.

  6. The Levels of the Lectin Pathway Serine Protease MASP-1 and Its Complex Formation with C1 Inhibitor Are Linked to the Severity of Hereditary Angioedema

    Hansen, Cecilie Bo; Csuka, Dorottya; Munthe-Fog, Lea; Varga, Lilian; Farkas, Henriette; Hansen, Karin Møller; Koch, Claus; Skjødt, Karsten; Garred, Peter; Skjoedt, Mikkel-Ole

    2015-01-01

    C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine proteases MASP-1 and MASP-2. Deficiency of C1-INH is associated with hereditary angioedema (HAE), an autosomal inherited disease characterized by swelling attacks caused by elevated levels of bradykinin. MASP...

  7. Hereditary angioedema in a Jordanian family with a novel missense mutation in the C1-inhibitor N-terminal domain.

    Jaradat, Saied A; Caccia, Sonia; Rawashdeh, Rifaat; Melhem, Motasem; Al-Hawamdeh, Ali; Carzaniga, Thomas; Haddad, Hazem

    2016-03-01

    Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) is an autosomal dominant disease caused by mutations in the SERPING1 gene. A Jordanian family, including 14 individuals with C1-INH-HAE clinical symptoms, was studied. In the propositus and his parents, SERPING1 had four mutations leading to amino acid substitutions. Two are known polymorphic variants (c.167T>C; p.Val34Ala and c.1438G>A; p.Val458Met), the others are newly described. One (c.203C>T; p.Thr46Ile) is located in the N-terminal domain of the C1-inhibitor protein and segregates with angioedema symptoms in the family. The other (c.800C>T; p.Ala245Val) belongs to the serpin domain, and derives from the unaffected father. DNA from additional 24 family members were screened for c.203C>T mutation in the target gene. All individuals heterozygous for the c.203C>T mutation had antigenic and functional plasma levels of C1-inhibitor below 50% of normal, confirming the diagnosis of type I C1-INH-HAE. Angioedema symptoms were present in 14 of 16 subjects carrier for the c.203T allele. Among these subjects, those carrying the c.800T variation had more severe and frequent symptoms than subjects without this mutation. This family-based study provides the first evidence that multiple amino acid substitutions in SERPING1 could influence C1-INH-HAE phenotype. PMID:26895475

  8. Treatment of hereditary angioedema with icatibant: efficacy in clinical trials versus effectiveness in the real-world setting.

    Maurer, Marcus; Longhurst, Hilary J; Fabien, Vincent; Li, H Henry; Lumry, William R

    2014-01-01

    Icatibant was efficacious and generally well tolerated for type I or II hereditary angioedema (HAE) attacks in adults in the phase III, randomized, placebo-controlled For Angioedema Subcutaneous Treatment (FAST)-3 trial. The Icatibant Outcome Survey (IOS) is an international, observational study assessing icatibant treatment of HAE attacks. We conducted a posthoc analysis to compare for the first time the treatment of HAE type I or II attacks in patients prescribed icatibant in real-world (IOS) versus controlled trial settings (FAST-3). In FAST-3, patients received icatibant administered by health care professionals (HCPs). In IOS, patients self-administered icatibant or were treated by HCPs. Median time to treatment, time to resolution (almost complete resolution [FAST-3] or complete resolution [IOS]), and attack duration in patients who were treated by an HCP were compared between IOS and FAST-3. Descriptive statistical methods compared nonlaryngeal attacks treated less than 12 hours from attack onset. Analysis included 102 patients (376 attacks) from IOS and 43 patients (43 attacks) from FAST-3 (controlled phase). All endpoints were significantly longer for patients in FAST-3 (HCP administration) versus IOS (HCP administration) (p III setting, with a shortened time to symptom resolution and attack duration. ClinicalTrials.gov NCT00912093 (FAST-3); NCT01034969 (IOS). PMID:25198193

  9. Hereditary angioedema: beyond international consensus - circa December 2010 - The Canadian Society of Allergy and Clinical Immunology Dr. David McCourtie Lecture

    Bowen Tom

    2011-02-01

    Full Text Available Abstract Background The 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema was published earlier this year in this Journal (Bowen et al. Allergy, Asthma & Clinical Immunology 2010, 6:24 - http://www.aacijournal.com/content/6/1/24. Since that publication, there have been multiple phase III clinical trials published on either prophylaxis or therapy of hereditary angioedema and some of these products have changed approval status in various countries. This manuscript was prepared to review and update the management of hereditary angioedema. Objective To review approaches for the diagnosis and management of hereditary angioedema (HAE circa December 2010 and present thoughts on moving from HAE management from international evidence-based consensus to facilitate more local health unit considerations balancing costs, efficacies of treatments, and risk benefits. Thoughts will reflect Canadian and international experiences. Methods PubMed searches including hereditary angioedema and diagnosis, therapy, management and consensus were reviewed as well as press releases from various pharmaceutical companies to early December 2010. Results The 2010 International Consensus Algorithms for the Diagnosis, Therapy and Management of Hereditary Angioedema is reviewed in light of the newly published phase III Clinical trials for prevention and therapy of HAE. Management approaches and models are discussed. Conclusions Consensus approach and double-blind placebo controlled trials are only interim guides to a complex disorder such as HAE and should be replaced as soon as possible with large phase IV clinical trials, meta analyses, data base registry validation of approaches including quality of life and cost benefit analyses, safety, and head-to-head clinical trials investigating superiority or non-inferiority comparisons of available approaches. Since not all therapeutic products are available in all jurisdictions

  10. Angioedema hereditario: Historia familiar y manifestaciones clínicas en 58 pacientes Hereditary angioedema: Family history and clinical manifestations in 58 patients

    Diego S. Fernández Romero

    2009-12-01

    Full Text Available El angioedema hereditario (AEH es una enfermedad rara, autosómica dominante, caracterizada por episodios de angioedema que comprometen la piel, el tracto gastrointestinal y la laringe. Analizamos las características epidemiológicas y clínicas en una serie de 58 pacientes, 53 (91% con diagnóstico de AEH tipo I y 5 (9% con tipo II. La edad media al inicio fue de 10.8 ± 9.5 años (0.1 a 59 y de 25.8 ± 16.2 años (2 a 77 en el momento del diagnóstico, con un retraso diagnóstico de 15.3 ± 14.3 años. El promedio de ataques en los 6 meses previos a la consulta fue de 7.4 ± 7.6 (0 a 40. Cincuenta y cuatro (93% presentaron ataques cutáneos, 50 (86% abdominales, 24 (41% laríngeos y 24 (41% cutáneos y abdominales combinados. Veintisiete (46.5% nunca utilizaron medicación preventiva para la enfermedad y 17 (29% recibieron danazol en diferentes dosis por diferentes periodos de tiempo. Durante los ataques, 15 (26% pacientes recibieron C1 inhibidor endovenoso alguna vez, 7 (12% recibieron plasma fresco y 40 (69% tratamiento sintomático. Ansiedad o situaciones de estrés y traumatismos fueron los desencadenantes más frecuentes. Identificamos a 6 (10% pacientes como primera mutación y a 52 (90% con historia familiar previa. Analizamos 20 troncos familiares identificando 205 individuos en riesgo de heredar la enfermedad, 109 (53% de ellos con síntomas o diagnóstico AEH. El total de individuos con síntomas de AEH fue de 145, de los cuales 19 (13% murieron por asfixia. Disminuir el retraso diagnóstico y ofrecer una terapéutica adecuada son desafíos a afrontar en el AEH.Hereditary angioedema (HAE is a rare autosomal dominant disease, characterized by episodes of edema typically involving the skin, gastrointestinal tract and larynx. We here describe the epidemiologic and clinical characteristic of a series of 58 patients with diagnosis of HAE, 53 (91% type I and 5 (9% type II. The mean age at first symptom was 10.8 ± 9.5 years and the mean

  11. Bradykinin-mediated angioedema.

    Obtułowicz, Krystyna

    2016-02-01

    Angioedema and urticaria often constitute a challenge in daily clinical practice. They may either co- -occur or present as independent conditions. They are characterized by a complex pathomechanism, and their symptoms may be triggered by diverse factors. These differences are crucial for developing a successful treatment regimen. Both conditions may have an allergic origin (immunoglobulin [Ig] E and non-IgE-related), usually induced by histamine, or a nonallergic one, such as bradykinin-mediated angioedema in patients with C1 inhibitor (C1-INH) deficiency or angioedema induced by certain drugs (eg, angiotensin-converting enzyme inhibitors). Currently, we distinguish 5 types of nonallergic angioedema: hereditary angioedema (HAE) due to C1-INH deficiency, acquired angioedema (AAE), and angioedema induced by the renin-angiotensin-aldosterone system, all of which are mediated by bradykinin, as well as pseudoallergic angioedema and idiopathic angioedema. Bradykinin-mediated angioedema (eg, laryngeal angioedema) may be life-threatening because of resistance to corticosteroids and antihistamine drugs. C1-INH concentrates are the drugs of choice in the treatment of HAE and AAE. In recent years, some new drugs have been introduced in the treatment of bradykinin-mediated angioedema, such as bradykinin B2-receptor antagonist, icatibant, and kallikrein inhibitor, ecallantide, which allow to improve treatment outcomes. PMID:26842379

  12. [Bradykinin-induced angioedema: Definition, pathogenesis, clinical presentation, diagnosis and therapy].

    Hahn, J; Bas, M; Hoffmann, T K; Greve, J

    2015-12-01

    The incidence of bradykinin-induced angioedema is considerably lower than that of histamine-induced forms; however, the same is true for the clinician's knowledge of this condition. Bradykinin-induced angioedemas include hereditary angioedema (HAE), as well as acquired forms induced by drugs or antibody formation, e.g., during the course of oncologic disease. Drug-induced forms affect almost exclusively the head and neck region, and are thus important for the otorhinolaryngologist. Clear differentiation between histamine-induced angioedema (e. g., connected to allergy/urticaria) and bradykinin-induced angioedema is essential for selection of the specific treatment and may be lifesaving. Antihistamines and cortisone derivatives have no relevant effect in bradykinin induced-angioedema, whereas blood-derived C1 esterase inhibitor and bradykinin receptor 2 antagonists represent effective therapeutic options--both for acute and prophylactic treatment. PMID:26597136

  13. F12-46C/T polymorphism as modifier of the clinical phenotype of hereditary angioedema.

    Speletas, M; Szilágyi, Á; Csuka, D; Koutsostathis, N; Psarros, F; Moldovan, D; Magerl, M; Kompoti, M; Varga, L; Maurer, M; Farkas, H; Germenis, A E

    2015-12-01

    The factors influencing the heterogeneous clinical manifestation of hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) represent one of the oldest unsolved problems of the disease. Considering that factor XII (FXII) levels may affect bradykinin production, we investigated the contribution of the functional promoter polymorphism F12-46C/T in disease phenotype. We studied 258 C1-INH-HAE patients from 113 European families, and we explored possible associations of F12-46C/T with clinical features and the SERPING1 mutational status. Given that our cohort consisted of related subjects, we implemented generalized estimating equations (GEEs), an extension of the generalized linear model accounting for the within-subject correlation. F12-46C/T carriers exhibited a significantly delayed disease onset (P < 0.001) and did not need long-term treatment (P = 0.02). In a GEE linear regression model, the presence of F12-46C/T was significantly associated with a 7-year delay in disease onset (P < 0.0001) regardless of SERPING1 mutational status. It is concluded that F12-46C/T carriage acts as an independent modifier of C1-INH-HAE severity. PMID:26248961

  14. Helicobacter pylori infection as a triggering factor of attacks in patients with hereditary angioedema

    Visy, Beáta; Füst, George; Bygum, Anette;

    2007-01-01

    BACKGROUND: Helicobacter pylori infection is considered among the causative factors of urticaria and angioedema. Having conducted a study on 65 patients, Hungarian authors reported in 2001 that successful eradication of H. pylori is followed by a significant reduction in the number of attacks in...... (> or = 5 per year) abdominal attacks was higher (p = .002) among the H. pylori-infected participants of the international study who underwent eradication as compared to the rest of patients. Successful eradication of H. pylori significantly (p = .0006) reduced the number of attacks in these patients as...... of frequent, edematous abdominal attacks may decrease substantially following the eradication of H. pylori from HAE patients infected with this pathogen. Therefore, screening of patients with HAE for H. pylori infection seems warranted. Eradication of H. pylori may lead to a marked reduction in...

  15. Non-histaminergic angioedema: focus on bradykinin-mediated angioedema.

    Busse, P J; Buckland, M S

    2013-04-01

    Angioedema is a result of increased vascular permeability, with subsequent extravasation of intravascular fluid into the surrounding tissues. Angioedema may be mediated by histamine, bradykinin or other mediators. Histaminergic angioedema generally presents with urticaria and/or pruritus and will respond to conventional treatment with antihistamines, corticosteroids or epinephrine. Bradykinin-mediated angioedema, which includes hereditary angioedema (HAE types I, II and III), acquired C1-INH deficiency, and angiotensin-converting enzyme inhibitor-induced angioedema does not typically present with urticaria/weals and does not respond to conventional agents such as antihistamines or corticosteroids. In recent years, several agents that prevent the generation or activity of bradykinin have been developed for the treatment of HAE types I and II and are also being evaluated in other types of bradykinin-mediated angioedema. These agents have the potential to improve outcomes for patients with different forms of bradykinin-mediated angioedema. PMID:23517034

  16. Acute and dramatic saxophone penis

    Carlota Gutiérrez García-Rodrigo

    2015-01-01

    Full Text Available We present a case of intense genital swelling because of a hereditary angioedema. This rare disease should be included in the differential diagnosis of acute and asymptomatic genital edema, because it may prevent future potentially life-threatening episodes of visceral angioedema.

  17. Refractory Angioedema in a Patient with Systemic Lupus Erythematosus

    Zahra Habibagahi

    2015-07-01

    Full Text Available Angioedema secondary to C1 inhibitor deficiency has been rarely reported to be associated with systemic lupus erythematosus. A genetic defect of C1 inhibitor produces hereditary angioedema, which is usually presented with cutaneous painless edema, but edema of the genital area, gastrointestinal and laryngeal tracts have also been reported. In lupus patients, angioedema may be the result of an acquired type of C1 inhibitor deficiency, most probably due to antibody formation directed against the C1 inhibitor molecule. Herein we report a new case of lupus nephritis that developed angioedema and a rapid course of disease progression with acute renal failure and alveolar hemorrhage without response to high dose steroid and plasmapheresis.

  18. Cutaneous necrosis in pregnancy secondary to activated protein C resistance in hereditary angioedema.

    Perkins, W; Downie, I; Keefe, M; Chisholm, M

    1995-04-01

    A 26-year-old woman with hereditary angineurotic oedema (HAE) presented at 22 weeks gestation with severe cutaneous necrosis similar to that seen in coumarin skin necrosis. Protein S deficiency secondary to HAE and pregnancy was postulated. Treatment with heparin, C1-inhibitor concentrates, systemic steroids and surgical debridement resulted in a successful outcome for both mother and child. Subsequent investigations revealed normal levels of protein C, antithrombin III, total protein S, free protein S but reduced function protein S activity with evidence of activated protein C resistance. Cutaneous necrosis has not been reported in associated with activated protein C resistance previously and the possible mechanisms are discussed. PMID:7745572

  19. Hereditary angioedema: Validation of the end point time to onset of relief by correlation with symptom intensity.

    Bernstein, Jonathan A; Ritchie, Bruce; Levy, Robyn J; Wasserman, Richard L; Bewtra, Againdra K; Hurewitz, David S; Obtułowicz, Krystyna; Reshef, Avner; Moldovan, Dumitru; Shirov, Todor; Grivcheva-Panovska, Vesna; Kiessling, Peter C; Keinecke, Heinz-Otto; Craig, Timothy J

    2011-01-01

    Time to onset of symptom relief in hereditary angioedema (HAE) is a common primary end point in clinical studies but it has never been validated by correlation with the course of HAE symptoms. This study was designed as a retrospective validation of the primary end point for a placebo-controlled phase II/III study in patients with HAE. Ninety-eight abdominal attacks were treated with 10 or 20 U/kg of a highly purified C1 esterase inhibitor (C1-INH) concentrate or placebo. The primary end point was the time to onset of symptom relief, as determined by the patients. Patients assessed the intensity of the symptoms of pain, nausea, vomiting, cramps, and diarrhea over time. By Spearman rank correlation, the primary end point was compared with the time to first reduction of (1) any symptom intensity, (2) the sum of symptom intensity scores, and (3) the intensity of the last symptom present at baseline. The C1-INH, 20 U/kg, and placebo groups were compared by one-sided two-sample Wilcoxon tests. The time to first reduction in intensity of the last symptom present at baseline had the highest correlation with the primary end point (r = 0.77). The time to onset of symptom relief and the time to the first reduction in intensity of the last symptom were significantly shorter for the C1-INH, 20 U/kg, group compared with placebo (p = 0.009 and p = 0.0036, respectively). The association with the intensity of single symptoms confirmed that the time to onset of symptom relief is an appropriate end point for assessing the efficacy of C1-INH therapy. PMID:21262096

  20. [Bradykinin mediated angioedema].

    Bouillet, L; Boccon-Gibod, I; Massot, C

    2011-04-01

    Bradykinin angioedema (AE) are characterized by acute recurrent episodes of localized swelling. They are not associated with pruritus or erythema, and are short-lived (24 to 72 hours), disappearing without any sequelae. Corticosteroids are useless. Skin or mucous membranes (upper respiratory and intestinal) could be affected. Bradykinin AE can be secondary to: (1) AE associated with C1 inhibitor deficiency (hereditary or acquired); (2) drug-induced AE (converting enzyme inhibitors…); (3) type III AE type (oestrogen dependant) without C1 inhibitor deficiency. These type III AE can be associated with a gain of function mutation that markedly increases factor XII activity. Prognosis depends on the laryngeal attacks (resulting in 25 % of death in the absence of specific treatment). In case of severe attacks, icatibant (bradykinin receptor antagonist) or C1 inhibitor concentrate can be used. In case of frequent attacks, long-term therapy with danazol or tranexamic acid is effective. PMID:20538389

  1. Factor XII mutations, estrogen-dependent inherited angioedema, and related conditions

    Binkley Karen E

    2010-07-01

    Full Text Available Abstract The clinical, biochemical and genetic features of the conditions known as estrogen-dependent inherited angioedema, estrogen-associated angioedema, hereditary angioedema with normal C-1 inhibitor, type III angioedema, or factor XII angioedema are reviewed. Discussion emphasizes pathogenesis, diagnosis, and management.

  2. Factor XII mutations, estrogen-dependent inherited angioedema, and related conditions.

    Binkley, Karen E

    2010-01-01

    The clinical, biochemical and genetic features of the conditions known as estrogen-dependent inherited angioedema, estrogen-associated angioedema, hereditary angioedema with normal C-1 inhibitor, type III angioedema, or factor XII angioedema are reviewed. Discussion emphasizes pathogenesis, diagnosis, and management. PMID:20667119

  3. Hereditary Angioedema Due to C1 Inhibitor Deficiency in Serbia: Two Novel Mutations and Evidence of Genotype-Phenotype Association

    Andrejević, Slađana; Korošec, Peter; Šilar, Mira; Košnik, Mitja; Mijanović, Radovan; Bonači-Nikolić, Branka; Rijavec, Matija

    2015-01-01

    Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease characterized by recurrent life-threatening oedemas and/or abdominal pain and caused by mutations affecting the C1 inhibitor gene, SERPING1. We sought to investigate the spectrum of SERPING1 mutations in Serbia and the possible genotype-phenotype association. C1-INH-HAE was diagnosed on the basis of clinical and laboratory criteria in 40 patients from 27 families; four were asymptomatic. Mutational analysis of the SERPING1 gene was performed by sequencing and multiplex ligation-dependent probe amplification. Disease-causing mutations in SERPING1 were identified in all patients. In C1-INH-HAE type I, we identified 19 different mutations, including 6 missense mutations, 6 nonsense mutations, 2 small deletions, 1 small insertion, 2 splicing defects and 2 large deletions. Two of the mutations (c.300C>T and c.1184_1185insTA) are reported here for the first time. All C1-INH-HAE type II patients from three families harboured the same substitution (c.1396C>T). Based on the type of mutation identified in the SERPING1 gene, patients were divided into two groups: group 1 (nonsense, frameshift, large deletions/insertions, splicing defect, and mutations at Arg444) or group 2 (missense, excluding mutations at Arg444). Significant differences were found in the clinical severity score (P = 0.005), prevalence of laryngeal (P = 0.040) and facial (P = 0.013) oedema, and long-term prophylaxis (P = 0.023) between the groups with different types of mutations. Because our population consisted of related subjects, differences in the severity score between mutation groups were further confirmed using the generalized estimating equation (P = 0.038). Our study identified 20 different disease-causing mutations, including two novel mutations, in all C1-INH-HAE patients, highlighting the heterogeneity of mutations in the SERPING1 gene. Furthermore, it appears that mutations with a clear effect

  4. Cricothyroidotomy in a angiotensin-converting enzyme (ACE Inhibitor tongue´s angioedema.

    Acle-Cervera L, Morales-Angulo C, García-Zornoza R, Rubio Suárez A

    2013-01-01

    Full Text Available Hereditary angioedema by inhibitors of Angiotensin Converting Enzyme(ACE is a very rare disorder. It usually affects the upper airway mucosa andproduce rapidly evolving acute exacerbations requiring urgent treatment.We repost the case of a patient being treated with ACE inhibitors and anreview of prevalence, pathophysiology and management of angioedemawith ACE inhibitors for treatment and the latest treatments.

  5. Angioedema from instant coffee

    Larkin, Kelly J.; Dvoretzky, Toban; Solomos, Nicholas J.

    2012-01-01

    Acute allergic angioedema is an abrupt-onset, unpredictable inflammatory reaction of the skin and mucous membranes. Without treatment, the condition may resolve within hours; however, when swallowing or breathing is affected, emergent medical attention is required. We report an atypical presentation of this condition, with a unique dietary cause. A 50-year-old man with no relevant medical history emergently presented with acute angioedema of the lower lip, without urticaria. The inflammation ...

  6. Development of a disease-specific quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-QoL: Spanish multi-centre research project

    Prior Nieves

    2012-07-01

    Full Text Available Abstract Background There is a need for a disease-specific instrument for assessing health-related quality of life in adults with hereditary angioedema due to C1 inhibitor deficiency, a rare, disabling and life-threatening disease. In this paper we report the protocol for the development and validation of a specific questionnaire, with details on the results of the process of item generation, domain selection, and the expert and patient rating phase. Methods/Design Semi-structured interviews were completed by 45 patients with hereditary angioedema and 8 experts from 8 regions in Spain. A qualitative content analysis of the responses was carried out. Issues raised by respondents were grouped into categories. Content analysis identified 240 different responses, which were grouped into 10 conceptual domains. Sixty- four items were generated. A total of 8 experts and 16 patients assessed the items for clarity, relevance to the disease, and correct dimension assignment. The preliminary version of the specific health-related quality of life questionnaire for hereditary angioedema (HAE-QoL v 1.1 contained 44 items grouped into 9 domains. Discussion To the best of our knowledge, this is the first multi-centre research project that aims to develop a specific health-related quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency. A preliminary version of the specific HAE-QoL questionnaire was obtained. The qualitative analysis of interviews together with the expert and patient rating phase helped to ensure content validity. A pilot study will be performed to assess the psychometric properties of the questionnaire and to decide on the final version.

  7. Complements Are Not Always a Good Thing: Novel Therapies for Angioedema.

    Bailey, Abby Mynatt; Reed, Brittany S; Weant, Kyle A; Justice, Stephanie Baker

    2016-01-01

    Hereditary angioedema attacks are rare, but emergency care providers must be aware of the clinical presentation and treatment of these patients because the emergency department remains the most common setting where these patients seek treatment. If providers are not aware of the past medical history of these patients, they are likely to receive standard therapies for respiratory distress and anaphylaxis including antihistamines, corticosteroids, and epinephrine. However, these medications may not work in these patients, given the pathophysiology of their underlying disease. Since 2009, several new therapies have been approved for the treatment of acute hereditary angioedema attacks. This article discusses pathophysiology, clinical presentation, and use of novel therapies for the management of angioedema. PMID:27139131

  8. Adverse events reported for hereditary angioedema medications: a retrospective study of spontaneous reports submitted to the EudraVigilance database, 2007-2013

    Aagaard L

    2016-05-01

    Full Text Available Lise Aagaard,1 Anette Bygum,2 1Section for Clinical Pharmacology, Institute of Public Health, Faculty of Health Sciences, University of Southern Denmark, 2Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark Abstract: Information about long-term safety issues from use of orphan drugs in treatment of hereditary angioedema (HAE is limited and must be studied further. As clinical trials in patients with rare diseases are limited, prescribers and patients have to rely on spontaneous adverse drug reaction (ADR reports for obtaining major information about the serious, rarely occurring, and unknown ADRs. In this study, we aimed to characterize ADRs reported for HAE medications in Europe from 2007 to 2013. ADR reports submitted for C1-inibitors and bradykinin receptor antagonists to the European ADR database, EudraVigilance (EV, were included in this study. The ADR reports were categorized with respect to age and sex of the patients, category of the reporter, type and seriousness of the reported ADRs, and medications. The unit of analysis was one adverse event (AE. Totally, 187 AEs were located in EV, and of these, 138 AEs were reported for Cinryze® (C1-inhibitor (73% of the total and 49 AEs for Firazyr® (icatibant (26% of the total AEs. Approximately 60% of all AEs were serious, including three fatal cases. Less than 5% of AEs were reported in children. In total, 62% of AEs were reported for women and 38% for men. For both Cinryze® and Firazyr®, the majority of reported AEs were of the type “general disorders and administration site conditions”. For Cinryze®, a large number of AEs of the type “HAE” and “drug ineffective” was reported, but only few of these were serious. For Firazyr®, several nonserious reports on injection site reactions were reported. In conclusion, this study showed that in EV, several ADR reports from use of HAE medications were identified, and a large number of these were

  9. Cinryze as the first approved C1 inhibitor in the USA for the treatment of hereditary angioedema: approval, efficacy and safety.

    Lunn, Michael; Santos, Carah; Craig, Timothy

    2010-01-01

    Hereditary angioedema (HAE) is a clinical disorder characterized by a deficiency of C1 esterase inhibitor (C1-INH). HAE has traditionally been divided into two subtypes. Unique among the inherited deficiencies of the complement system, HAE Types I and II are inherited as an autosomal dominant disorder. The generation of an HAE attack is caused by the depletion and/or consumption of C1-inhibitor manifested as subcutaneous or submucosal edema of the upper airway, face, extremities, or gastrointestinal tract. Attacks can be severe and potentially life-threatening, particularly with laryngeal involvement. Despite the availability of C1-INH for the treatment of HAE since the 1980s in Europe and other countries, HAE treatment in the United States was limited to androgen therapy. The human plasma-derived C1 esterase inhibitor (Cinryze™), distributed by Lev Pharmaceuticals, was approved in October 2008 for the prevention of HAE attacks based on the results of a phase III clinical trial. This review aims to describe the history of C1-INH replacement in HAE as well as the pharmacology, efficacy and safety of C1-INH, concentrating on Cinryze as the first approved chronic replacement treatment for the prophylaxis of HAE attacks. PMID:22282695

  10. International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency

    Caballero, Teresa; Farkas, Henriette; Bouillet, Laurence;

    2012-01-01

    section. Regional anesthesia is preferred to endotracheal intubation. Breast cancer: Attenuated androgens should be avoided. Antiestrogens can worsen angioedema symptoms. In these cases anastrozole might be an alternative. Other issues addressed include special features of HAE-C1-INH treatment in female...... patients, genetic counseling, infertility, abortion, lactation, menopause treatment, and endometrial cancer. CONCLUSIONS: A consensus for the management of female patients with HAE-C1-INH is presented....... devices, and progestins can be used. Pregnancy: Attenuated androgens are contraindicated and should be discontinued before attempting conception. Plasma-derived human C1 inhibitor concentrate (pdhC1INH) is preferred for acute treatment, short-term prophylaxis, or long-term prophylaxis. Tranexamic acid...

  11. A Nationwide Study of Norwegian Patients with Hereditary Angioedema with C1 Inhibitor Deficiency Identified Six Novel Mutations in SERPING1

    Johnsrud, Irene; Kulseth, Mari Ann; Rødningen, Olaug Kristin; Landrø, Linn; Helsing, Per; Waage Nielsen, Erik; Heimdal, Ketil

    2015-01-01

    Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is characterized by relapsing, non-pruritic swelling in skin and submucosal tissue. Symptoms can appear in early infancy when diagnosis is more difficult. In the absence of a correct diagnosis, treatment of abdominal attacks often lead to unnecessary surgery, and laryngeal edema can cause asphyxiation. A cohort study of 52 patients from 25 unrelated families in Norway was studied. Diagnosis of C1-INH-HAE was based on international consensus criteria including low functional and/or antigenic C1-INH values and antigenic C4. As SERPING1 mutations in Norwegian patients with C1-INH-HAE are largely undescribed and could help in diagnosis, we aimed to find and describe these mutations. Mutation analysis of the SERPING1 gene was performed by Sanger sequencing of all protein coding exons and exon-intron boundaries. Samples without detected mutation were further analyzed by multiplex ligation-dependent probe amplification to detect deletions and duplications. Novel mutations suspected to lead to splice defects were analyzed on the mRNA level. Fifty-two patients from 25 families were included. Forty-four (84,6%) suffered from C1-INH-HAE type I and eight (15,4%) suffered from C1-INH-HAE type II. Pathogenic or likely pathogenic mutations were found in 22/25 families (88%). Thirteen unique mutations were detected, including six previously undescribed. There were three missense mutations including one mutation affecting the reactive center loop at codon 466, three nonsense mutations, three small deletions/duplications, three gross deletions, and one splice mutation. PMID:26154504

  12. The Levels of the Lectin Pathway Serine Protease MASP-1 and Its Complex Formation with C1 Inhibitor Are Linked to the Severity of Hereditary Angioedema.

    Hansen, Cecilie Bo; Csuka, Dorottya; Munthe-Fog, Lea; Varga, Lilian; Farkas, Henriette; Hansen, Karin Møller; Koch, Claus; Skjødt, Karsten; Garred, Peter; Skjoedt, Mikkel-Ole

    2015-10-15

    C1 inhibitor (C1-INH) is known to form complexes with the lectin complement pathway serine proteases MASP-1 and MASP-2. Deficiency of C1-INH is associated with hereditary angioedema (HAE), an autosomal inherited disease characterized by swelling attacks caused by elevated levels of bradykinin. MASP-1 was shown to cleave high m.w. kininogen into bradykinin; therefore, we hypothesized that MASP-1 levels and the quantity of MASP-1/C1-INH complexes might be associated with different paraclinical and clinical outcomes of HAE. We measured MASP-1 serum concentrations and endogenous MASP-1/C1-INH complex levels in 128 HAE patients and 100 controls. Relatively high levels of pre-existing MASP-1/C1-INH complexes were observed in normal serum, and we found that both the serum levels of MASP-1 and the complex formation between MASP-1 and C1-INH were significantly reduced in HAE patients compared with matched controls (p < 0.0001). The level of MASP-1 and MASP-1/C1-INH complexes in HE patients correlated with the level of C1-INH (p = 0.0009 and p = 0.0047, respectively), the level of C4 (p = 0.0084 and p < 0.0001, respectively), and the number of attacks in the year of blood sampling (p = 0.0075 and p = 0.0058, respectively). In conclusion, we show that MASP-1/C1-INH complexes circulate in normal human blood. The levels of MASP-1 and MASP-1/C1-INH complexes are reduced in HAE patients compared with controls. Both MASP-1 and MASP-1/C1-INH complexes are related to the degree of complement C4 consumption, as well as the severity of disease. These results suggest that MASP-1 may exert a previously unrecognized role in the pathophysiology of HAE. PMID:26371246

  13. C1-inhibitor (C1-INH) autoantibodies in hereditary angioedema. Strong correlation with the severity of disease in C1-INH concentrate naïve patients.

    Varga, Lilian; Széplaki, Gábor; Visy, Beáta; Füst, George; Harmat, George; Miklós, Katalin; Németh, Julianna; Cervenak, László; Karádi, István; Farkas, Henriette

    2007-02-01

    The presence of autoantibodies to C1-inhibitor (C1-INH-Abs) is a hallmark of acquired C1-inhibitor deficiency. However, only scarce data are available on their prevalence in hereditary angioedema (HAE). In a prospective study performed between 2001 and 2004 in 95 patients with Type I or II HAE, serum samples were taken one to three times a year and clinical status of the patients was registered. Serum samples were tested for total activity of the classical pathway, C1q, C3, C4 and C1-inhibitor (C1-INH) concentration and activity levels, as well as the presence of IgG, IgA and IgM type anti-C1-inhibitor antibodies (C1-INH-Ab). Fifty-four healthy age and gender matched persons served as control. Significant differences between the patients and controls in the occurrence of elevated (2S.D. higher than mean of control) C1-INH-Abs titers was found only in the case of IgM type C1-INH-Abs. Elevated (>4.22AU/ml) IgM C1-INH-Abs levels were found in 31 and 4% of the patients and controls, respectively (p<0.001). Surprisingly, high titer IgM C1-INH-Abs were present with equal frequency in the 41 HAE patients ever treated with C1-INH concentrate and in the 54 C1-INH treatment naïve patients. In the latter group, strong positive correlation between the levels of the IgM C1-INH-Abs and the most severe disease (score 1) (p=0.0021) and the yearly attack rate (p=0.0173) were obtained. In addition, the levels of the IgM C1-INH-Abs exhibited strong negative correlation to the C1-inhibitor concentration and functional activity, total classical complement pathway activity, and a positive correlation to total IgM concentration. Taken together, these data indicate that IgM type C1-INH-Abs are present with highly elevated frequency in HAE patients irrespectively of the previous treatment with C1-INH concentrate. Most probable production of these autoantibodies is the consequence of the activation of complement and other plasma enzyme systems during HAE attacks. Determination of IgM C1

  14. 86 The Efficacy and Safety of Human Plasma-derived C1-Inhibitor Concentrate Administered for the Treatment of Attacks in Pediatric Patients with Hereditary Angioedema Due to C1-Inhibitor Deficiency

    Farkas, Henriette; Csuka, Dorottya; Zotter, Zsuzsanna; Szabó, Erika; Kelemen, Zsuzsanna; Varga, Lilian; Fejes, János; Harmat, George

    2012-01-01

    Background Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a life-threatening, rare disease characterized by recurrent edematous attacks. In 50% of cases, the initial onset of symptoms occurs between 5 and 11 years of age. There are limited data on the emergency treatment of acute episodes in pediatric patients. Our aim was to analyze the efficacy and safety of human plasma-derived C1-INH concentrate in our pediatric patient population with HAE-C1-INH. Methods 50 pediatric patients (23 boys, 27 girls; 45 HAE type I, 5 HAE type II patients) were enrolled. The follow-up period began at the time of diagnosis and ended when the patient turned 18 years old. The indications for the use of C1-INH concentrate were upper airway oedema of any severity; moderate-to-severe abdominal edema; edema of face, neck, or lips and severe edema of the extremities and trunk. Clinical and laboratory data were entered into the Hungarian HAE Registry. Results 152 attacks out of 1392 experienced by 42 patients were treated with C1-INH concentrate (28% of attacks at home and 72% at the clinic). The distribution of C1-INH-treated attacks by location was as follows: 38% subcutaneous, 32% abdominal, 30% upper airway. In all locations, the clinical symptoms were consistently relieved by 500 IU C1-INH concentrate. An additional 500 IU dose of C1-INH concentrate was required in 4 cases only. The symptoms improved within 15 to 60 minutes of drug administration. Time to complete resolution was 24 to 48 hours in subcutaneous edema, 12 to 24 hours in abdominal attacks, and less than 12 hours when the edema involved the upper airways. No progression or recurrence of the attack was observed. Repeated administration did not reduce therapeutic efficacy of the drug. Adverse events did not occur. Transmission of viral infections (HIV, HBV, HBC, Parvo virus B19) was not detected. Comparing the first and last year of follow-up, anti-C1-INH antibodies (IgA, IgG, IgM types) did not show any

  15. [Angioedema and urticaria].

    Boccon-Gibod, I; Bouillet, L

    2014-11-01

    Angiœdema (AE) is the clinical expression of urticaria (U) which occurs when urticaria is located within the subcutis. It is a syndrome characterized by a sudden and limited subcutaneous and/or submucous swelling. The updated classification of urticaria distinguishes acute and chronic urticaria. Chronic urticaria is spontaneous (CSU) or inducible (CIU). Angioedema in chronic urticaria is rarely allergic, but most of the time caused by a non-specific histamine release from activated mast-cell (non IgE mediated reaction). Angioedemas are recurrent, concomitant or not with wheals. They appear skin-coloured, sometimes slightly rosy, non-inflammatory, and more painful than itchy. They are transient, ephemeral, migrant, last most of the time a few hours (< 24 or 48h) and disappear without after-effects. They are considered "deep urticaria" and wheals "superficial urticaria". When AE or wheals last more than 6 weeks (with or without free intermission), it is called chronic urticaria. Angioedema can be elicited or worsened by physical factors (cold urticaria, exercise, heat, solar, vibratory, aquagenic, delayed pressure urticaria…) and /or drugs (as aspirin, nonsteroid anti-inflammatory drugs, morphine, antibiotics…). The treatment of histaminergic angioedemas of chronic urticaria is based on modern second generation antihistamines (anti H1). In allergic acute urticaria only, additional treatment for anaphylaxis can be used if needed (grade 2 to 4). In chronic urticaria, steroids should be avoided : they can make symptoms worse and long-lasting because of corticosteroid dependence. PMID:25539680

  16. Self-administration of C1-inhibitor concentrate in patients with hereditary or acquired angioedema caused by C1-inhibitor deficiency

    Levi, M; Choi, G; Picavet, C; Hack, CE

    2006-01-01

    Background: Administration of C1-inhibitor concentrate is effective for prophylaxis and treatment of severe angioedema attacks caused by Cl-inhibitor deficiency. The concentrate should be administered intravenously and hence needs to be administered by health care professionals, which might cause co

  17. Using Fresh Frozen Plasma for Acute Airway Angioedema to Prevent Intubation in the Emergency Department: A Retrospective Cohort Study

    Aya Saeb

    2016-01-01

    Full Text Available Background. Angioedema (AE is a common condition which can be complicated by laryngeal edema, having up to 40% mortality. Although sporadic case reports attest to the benefits of fresh frozen plasma (FFP in treating severe acute bouts of AE, little evidence-based support for this practice is available at present. Study Objectives. To compare the frequency, duration of intubation, and length of intensive care unit (ICU stay in patients with acute airway AE, with and without the use of FFP. Methods. A retrospective cohort study was conducted, investigating adults admitted to large community hospital ICU with a diagnosis of AE during the years of 2007–2012. Altogether, 128 charts were reviewed for demographics, comorbidities, hospital courses, and outcomes. A total of 20 patients received FFP (108 did not. Results. Demographics and comorbidities did not differ by treatment group. However, nontreated controls did worse in terms of intubation frequency (60% versus 35%; p=0.05 and ICU stay (3.5 days versus 1.5 days; p<0.001. Group outcomes were otherwise similar. Conclusion. In an emergency department setting, the use of FFP should be considered in managing acute airway nonhereditary AE (refractory to steroid, antihistamine, and epinephrine. Larger prospective, better controlled studies are needed to devise appropriate treatment guidelines.

  18. Acutely Onset Amiodarone-Induced Angioedema in a Patient with New Atrial Fibrillation

    Hossein Vakili

    2014-01-01

    Full Text Available A 50-year-old man was admitted to our emergency department due to new episode of palpitation. He had history of angioplasty of right coronary artery (RCA with drug eluting stent 2 years ago. His electrocardiogram revealed atrial fibrillation (AF. Intravenous amiodarone 150 mg during 10 minutes and then 1 mg/min infusion were started to achieve rate control and pharmacologic conversion to sinus rhythm. After 60 minutes of starting amiodarone infusion, he developed swelling of the skin around his mouth and eyes, and also mucosa of the mouth, eyes and tongue. To conclude, angioedema should be considered a rare side effect of amiodarone which is used broadly in cardiovascular field.

  19. Acquired angioedema secondary to hormone replacement therapy

    Malani Kumar

    2005-10-01

    Full Text Available Angioedema is a potentially life threatening condition and may be either inherited or acquired. The latter is rare with only a handful of cases reported in the world literature. Presenting complaints are often vague. Those most commonly described include swelling in the subcutaneous and submucosal tissues. Patients presenting with laryngeal edema have high mortality, and high clinical suspicion is necessary to avoid instrumentation, which can precipitate laryngeal spasm. We present a review of reported cases of hormonally induced hereditary angioedema, along with a report of a patient with acquired angioedema secondary to hormone replacement therapy. To the best of our knowledge, this case probably represents the first reported case of acquired angioedema secondary to hormone replacement therapy.

  20. Diagnosis and treatment of bradykinin-mediated angioedema: outcomes from an angioedema expert consensus meeting.

    Craig, Timothy J; Bernstein, Jonathan A; Farkas, Henriette; Bouillet, Laurence; Boccon-Gibod, Isabelle

    2014-01-01

    Several types of angioedema exist beyond hereditary angioedema (HAE) types I/II; however, the diagnostic and treatment needs of these conditions are not well understood. Noticeably, there are no licensed treatments available for other forms of angioedema beyond HAE types I/II, and similarly they are unresponsive to conventional antihistamine/glucocorticoid treatment. A group of angioedema experts met in Budapest in May 2013 to discuss such issues, presenting their experience, reviewing available literature and identifying unmet diagnostic and treatment needs in three different angioedema types: HAE with normal C1-inhibitor (C1-INH; previously referred to as type III HAE); nonallergic angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema (ACEI-AAE), and acquired angioedema due to C1-INH deficiency (C1-INH-AAE). The group identified unmet diagnostic and treatment needs in HAE-nC1-INH, C1-INH-AAE and ACEI-AAE, explored remedies and made recommendations on how to diagnose and treat these forms of angioedema. The group discussed the difficulties associated with using diagnostic markers, such as the level and function of C1-INH, C1q and C4 to reliably diagnose the angioedema type, and considered the use of genetic testing to identify mutations in FXII or XPNPEP2 that have been associated with HAE-nC1-INH and ACEI-AAE, respectively. Due to the lack of approved treatments for HAE-nC1-INH, ACEI-AAE and C1-INH-AAE, the group presented several case studies in which therapies approved for treatment of HAE types I/II, such as icatibant, ecallantide and pasteurized, nanofiltered C1-INH, were successful. It was uniformly agreed that further studies are needed to improve the diagnosis and treatment of angioedema other than HAE types I/II. PMID:25401373

  1. Hereditary angioderma: an uncommon cause of acute abdomen. Abdominal computed tomography and ultrasound findings

    We present an uncommon case of acute abdomen in a patient with hereditary angioderma. The ultrasound and CT findings described may suggest this diagnosis, thus avoiding useless surgical interventions in patients in whom the disease has not been previously diagnosed. (Author) 19 refs

  2. Classification, diagnosis, and approach to treatment for angioedema

    Cicardi, M; Aberer, W; Banerji, A; Bas, M; Bernstein, J A; Bork, K; Caballero, T; Farkas, H; Grumach, A; Kaplan, A P; Riedl, M A; Triggiani, M; Zanichelli, A; Zuraw, B; Bygum, Anette

    2014-01-01

    Angioedema is defined as localized and self-limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have an...... and three types of hereditary angioedema were identified as separate forms from the analysis of the literature and were presented in detail at the meeting. Here, we summarize the analysis of the data and the resulting classification of angioedema.......Angioedema is defined as localized and self-limiting edema of the subcutaneous and submucosal tissue, due to a temporary increase in vascular permeability caused by the release of vasoactive mediator(s). When angioedema recurs without significant wheals, the patient should be diagnosed to have...... angioedema as a distinct disease. In the absence of accepted classification, different types of angioedema are not uniquely identified. For this reason, the European Academy of Allergy and Clinical Immunology gave its patronage to a consensus conference aimed at classifying angioedema. Four types of acquired...

  3. Acebrophylline-induced angioedema

    Sanitha Kuriachan

    2015-01-01

    Full Text Available A 53-year-old woman visited her physician complaining of acute breathlessness and productive cough. Her medications included budesonide and formoterol for asthma, fixed-dose combination aspirin 150 mg + clopidogrel 75 mg + atorvastatin 20 mg for ischemic heart disease. History revealed that she had allergic rhinitis and was hypersensitive to penicillins. The patient was prescribed acebrophylline (ABP. Six hours after ABP therapy she presented with generalized urticarial lesions, swelling of hands, feet, lips and face, suggestive of angioedema. ABP was stopped immediately, and the patient was treated symptomatically. This case was categorized as probable as per standard causality assessment scale.

  4. Angioedema Due to use of ACE-Inhibitor

    Hulya Eyigor

    2014-03-01

    Full Text Available       Angioedema; which may be hereditary or non-hereditary, is defined as a sudden, severe, often in awkward, temporary swelling of skin, subcutaneous and mucous membranes of the face, tongue, lip, larynx, and gastrointestinal areas. Angiotensin Converting Enzyme (ACE inhibitor drugs are widely used in essential hypertension and congestive heart diseases and effective and safe drugs. Angioedema is quite rare due to the use of ACE inhibitors, the rate changes from 0.1 to 0.7% reported in the literature. The pathophysiology of angioedema induced by ACE inhibitors are not completely understood, this situation has been tought to be associated with an increased activity of bradykinin related vasodilatation, increased vascular permeability and interstitial edema. In this study, a case of 65-year-old male patient presented angioedema induced by lisinopril was presented and a very rare side effect of ACE inhibitor drugs was reviewed with the relevant literature.

  5. Conestat alfa for the treatment of angioedema attacks

    Davis B

    2011-07-01

    Full Text Available Benjamin Davis, Jonathan A BernsteinUniversity of Cincinnati College of Medicine, Department of Internal Medicine, Division of Immunology/Allergy Section, Cincinnati, OH, USAAbstract: Recently, multiple C1 inhibitor (C1-INH replacement products have been approved for the treatment of hereditary angioedema (HAE. This review summarizes HAE and its current treatment modalities and focuses on findings from bench to bedside trials of a new C1-INH replacement, conestat alfa. Conestat alfa is unique among the other C1-INH replacement products because it is produced from transgenic rabbits rather than derived from human plasma donors, which can potentially allow an unlimited source of drug without any concern of infectious transmission. The clinical trial data generated to date indicate that conestat alfa is safe and effective for the treatment of acute HAE attacks.Keywords: androgens, adverse events, patients, HAE attacks 

  6. Angioedema due to Systemic Isotretinoin Therapy

    Pelin Üstüner

    2014-01-01

    Full Text Available Angioedema is the swelling of the mucosal membranes as a variant of urticaria induced by hereditary C1 esterase inhibitor enzyme deficiency, certain foods, or drugs. Herein, we report the case of a 23-year-old woman, with mild-moderate acne presenting with widespread facial angioedema on the 2nd day of systemic isotretinoin treatment. The patient had taken no drugs other than isotretinoin in the preceding days and had no known food allergy. Her angioedema was resolved after the isotretinoin was discontinued. We want to draw the attention of dermatologists to this rare adverse allergic effect of isotretinoin which is frequently used in the treatment of acne vulgaris.

  7. Radiologic manifestations of angioedema

    Ishigami, Kousei; Averill, Sarah L.; Pollard, Janet H.; McDonald, Joshua M.; Sato, Yutaka

    2014-01-01

    Objectives The purpose of this pictorial review is to present imaging findings of angioedema involving the various organs. Conclusion The role of imaging for patients with angioedema includes the evaluation of the upper airway for obstruction and the exclusion of other possible aetiologies, such as neoplastic or infectious processes. Glossomegaly is a common finding of head and neck angioedema. Angioedema may involve organ systems beyond the superficial regions and the head and neck including...

  8. Treatment of hereditary angioedema with nanofiltered C1-esterase inhibitor concentrate (Cetor®): multi-center phase II and III studies to assess pharmacokinetics, clinical efficacy and safety.

    Hofstra, J J; Kleine Budde, I; van Twuyver, E; Choi, G; Levi, M; Leebeek, F W G; de Monchy, J G R; Ypma, P F; Keizer, R J; Huitema, A D R; Strengers, P F W

    2012-03-01

    From 1997, plasma-derived C1-inhibitor concentrate (Cetor®) has been available to HAE and AAE patients. Recently, a virus reducing 15 nm nanofiltration step has been introduced in the production process. A randomized, double-blind controlled cross-over study was performed to compare the pharmacokinetics (PK) of nanofiltered (C1-INH-NF) with conventional C1-inhibitor (C1-INH). Efficacy and safety were investigated in an open-label, on-demand and a prophylactic study. No differences in pharmacokinetic parameters between C1-INH and C1-INH-NF were found (13 non-symptomatic HAE patients). Both C1-inhibitor products equally increased plasma C4 levels. In the on-demand study, 14 acute angioedema attacks in 8 patients were analyzed. In the prophylactic study, 1 AAE and 5 HAE patients experienced in total 31 attacks during 748 observation days. In total 180,000 units of C1-INH-NF were administered. No product-related adverse events occurred, and no anti-C1-antibodies were induced. Nanofiltration in the production process of C1-inhibitor did not affect the pharmacokinetics, efficacy, and safety. PMID:22197071

  9. Recurrent angioedema and urticaria.

    Bishop, P C; Wisnieski, J J; Christensen, J

    1993-01-01

    The case reported here illustrates the life-threatening aspects of angioedema and the need to thoroughly investigate the possible causes of this clinical finding. As discussed, the causes of angioedema are numerous. Commonly implicated in drug-induced angioedema are antihypertensive ACE inhibitor drugs, as was originally thought with this patient. Because of her skin lesions and macrocytic anemia, further studies were done. These studies led to a diagnosis of hypocomplementemic urticarial vas...

  10. Angioedema Associated with Haloperidol

    AlMadhyan, Abdulmajeed Brahim

    2015-01-01

    Haloperidol is one of the antipsychotic medications which are widely used in the emergency department and its association with angioedema which is very rarely reported in scientific literature. One of the serious situations in the emergency department is angioedema and it bends airway obstruction which is need early attention and treatment. A case was reported which was observed at a governmental hospital in Riyadh. An adult female developed angioedema after single dose of Haloperidol intramu...

  11. Recurrent angioedema and urticaria.

    Bishop, P C; Wisnieski, J J; Christensen, J

    1993-11-01

    The case reported here illustrates the life-threatening aspects of angioedema and the need to thoroughly investigate the possible causes of this clinical finding. As discussed, the causes of angioedema are numerous. Commonly implicated in drug-induced angioedema are antihypertensive ACE inhibitor drugs, as was originally thought with this patient. Because of her skin lesions and macrocytic anemia, further studies were done. These studies led to a diagnosis of hypocomplementemic urticarial vasculitis syndrome, an uncommon to rare form of acquired angioedema, urticarial vasculitis, arthritis, and obstructive airway disease associated with the production of autoantibodies to C1q. It is an autoimmune disorder related to but separate from SLE. PMID:8279170

  12. Angiotensin Converting Enzyme Inhibitor-related Angioedema: A Case of an Unexpected Death

    Eray Atalay

    2015-11-01

    Full Text Available Angioedema is an asymmetric non-pitting oedema on face, lips, tongue and mucous membranes; any delay in diagnosis and treatment can be fatal. Treatment with lisinopril as an angiotensin converting enzyme (ACE inhibitor, can be a reason of angioedema. Here we report a case who developed oral-facial edema four years after using lisinopril/hydrochlorothiazide. Laryngeal oedema is a main cause of death in angioedema. The treatment of choice in angioedema including fresh frozen plasma, C1 inhibitor concentrations and BRK-2 antagonists (bradykinin B2 receptor antagonists were used. In this case; a 77 years old female patient suffering from hypertension was considered. This patient was suffering two days from swelling on her face and neck. Non- allergic angioedema was distinguished in five major forms; acquired (AAO, hereditary (HAE, renin-angiotensin-aldosterone system (RAAS blocker-dependent, pseudoallergic angioedema (PAS and an idiopathic angioedema (IAO. She was admitted to our clinic with the diagnosis of hereditary angioedema. Patient had skin edema and life threatening laryngeal edema. In emergency department treatment was started using intravenous methylprednisolone, diphenydramine as well as inhaled and subcutaneous epinephrine simultaneously. Despite the initial treatment, the patient died due to the insufficient respiration and cardiac arrest. The patient has no history of kidney disease.

  13. Angiotensin Converting Enzyme Inhibitor-related Angioedema: A Case of an Unexpected Death.

    Atalay, Eray; Özdemir, Mehmet Tamer; Çiğsar, Gülşen; Omurca, Ferhat; Aslan, Nurullah; Yildiz, Mehmet; Gey, Zehra Bahar

    2015-11-01

    Angioedema is an asymmetric non-pitting oedema on face, lips, tongue and mucous membranes; any delay in diagnosis and treatment can be fatal. Treatment with lisinopril as an angiotensin converting enzyme (ACE) inhibitor, can be a reason of angioedema. Here we report a case who developed oral-facial edema four years after using lisinopril/hydrochlorothiazide. Laryngeal oedema is a main cause of death in angioedema. The treatment of choice in angioedema including fresh frozen plasma, C1 inhibitor concentrations and BRK-2 antagonists (bradykinin B2 receptor antagonists) were used. In this case; a 77 years old female patient suffering from hypertension was considered. This patient was suffering two days from swelling on her face and neck. Non- allergic angioedema was distinguished in five major forms; acquired (AAO), hereditary (HAE), renin-angiotensin-aldosterone system (RAAS) blocker-dependent, pseudoallergic angioedema (PAS) and an idiopathic angioedema (IAO). She was admitted to our clinic with the diagnosis of hereditary angioedema. Patient had skin edema and life threatening laryngeal edema. In emergency department treatment was started using intravenous methylprednisolone, diphenydramine as well as inhaled and subcutaneous epinephrine simultaneously. Despite the initial treatment, the patient died due to the insufficient respiration and cardiac arrest. The patient has no history of kidney disease. PMID:26725563

  14. Angioedema: Clinical Presentations and Pharmacological Management.

    Collins-Yoder, Angela Smith

    2016-01-01

    Angioedema (AE) is a unique clinical presentation of an unchecked release of bradykinin. The origin of this clinical presentation can be either genetic or acquired. The outcome within the patient is subcutaneous swelling of the lower layers of the epidermis. Symptoms are most often localized to the upper airway or the gastrointestinal tract. A typical course resolves in 5 to 7 days, but in some patients, the clinical manifestations exist up to 6 weeks. Hereditary AE is rare and genetically linked, and typically, the patient has episodes for many years before diagnosis. Episodes of acquired AE may be drug induced, triggered by a specific allergen, or idiopathic. Angioedema can elicit the need for critical care interventions, for advanced airway management, or unnecessary abdominal surgery. The treatment for these patients is evolving as new pharmacological agents are developed. This article addresses subtypes of AE, triggers, pharmacology, and information for interdisciplinary team planning of individualized case management. PMID:27258954

  15. Angioedema associated with Crohn's disease: Response to biologics

    Flavio Habal; Vivian Huang

    2012-01-01

    A 46-year-old female patient with terminal ileum Crohn's disease and ankylosing spondylitis presented with recurrent angioedema and urticaria.Investigations ruled out hereditary angioedema,and environmental or food allergen triggers.She was diagnosed with chronic idiopathic urticaria with angioedema,and was treated with a trial of intravenous immunoglobulin immunotherapy,danazol,prednisone and hydroxyzine.Due to ongoing bowel and arthritic complaints,she was started on infliximab infusions and within 2 treatments,she had complete resolution of the angioedema and urticaria,as well as of the bowel and arthritic symptoms.Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor (TNF)-α agent,adalimumab.Since then,she has had no further angioedema or urticaria,and her Crohn's disease has been quiescent.This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn's disease that was successfully treated with anti-TNF-α agents.

  16. The humanistic burden of hereditary angioedema

    Caballero, Teresa; Aygören-Pürsün, Emel; Bygum, Anette;

    2014-01-01

    extremities; 24% experienced an attack in more than one site. The impact of HAE on daily activities was high during attacks and did not vary significantly by body site affected; patients also reported that HAE impacted their daily activities between attacks. Patients reported substantial anxiety about future...... attacks, traveling, and passing HAE to their children. Based on Hospital Anxiety and Depression Scale scores, 38 and 14% had clinically meaningful anxiety and depression, respectively. Despite standard of care, HAE patients still have frequent and painful attacks. Patients experience substantial...

  17. Burden of Illness in Hereditary Angioedema

    Bygum, Anette; Aygören-Pürsün, Emel; Beusterien, Kathleen;

    2015-01-01

    attacks, and passing HAE to children, reduced work/school productivity, and limited career/educational achievement. Patient caregivers also experienced worry and work/activity interruption during the attacks. In conclusion, a conceptual model was developed illustrating the hypothesized relationships among...

  18. Hereditary pancreatitis

    Richard M Charnley

    2003-01-01

    Hereditary pancreatitis is an autosomal dominant condition,which results in recurrent attacks of acute pancreatitis,progressing to chronic pancreatitis often at a young age.The majority of patients with hereditary pancreatitis expressone of two mutations (R122H or N29I) in the cationictrypsinogen gene (PRSS1 gene). It has been hypothesisedthat one of these mutations, the R122H mutation causespancreatitis by altering a trypsin recognition site sopreventing deactivation of trypsin within the pancreas andprolonging its action, resulting in autodigestion. Families withthese two mutations have been identified in many countriesand there are also other rarer mutations, which have alsobeen linked to hereditary pancreatitis.Patients with hereditary pancreatitis present in the sameway as those with sporadic pancreatitis but at an earlierage. It is common for patients to remain undiagnosed formany years, particularly ifthey present with non-specificsymptoms. Hereditary pancreatitis should always beconsidered in patients who present with recurrent pancreatitiswith a family history of pancreatic disease. If patients withthe 2 common mutations are compared, those with theR122H mutation are more likely to present at a younger ageand are more likely to require surgical intervention than thosewith N29I. Hereditary pancreatitis carries a 40 % lifetimerisk of pancreatic cancer with those patients aged between50 to 70 being most at risk in whom screening tests maybecome important.

  19. Angioedema due to Pomegranate: Original Image

    Meliha Findik

    2014-01-01

     Acute allergic angioedema is an abrupt-onset, unpredictable inflammatory reaction of the skin and mucous membranes. A 35-year-old female patient presented to our emergency department with redness on the cheeks and edema in her mouth and eyelids. It was learned from the history that her symptoms were begun 15 minutes after eating a pomegranate. 40 mg methylprednisolone and 50 mg diphenhydramine were administered intravenously.

  20. Angioedema due to Pomegranate: Original Image

    Meliha Findik

    2014-03-01

    Full Text Available  Acute allergic angioedema is an abrupt-onset, unpredictable inflammatory reaction of the skin and mucous membranes. A 35-year-old female patient presented to our emergency department with redness on the cheeks and edema in her mouth and eyelids. It was learned from the history that her symptoms were begun 15 minutes after eating a pomegranate. 40 mg methylprednisolone and 50 mg diphenhydramine were administered intravenously.

  1. Angioedema: Diagnosis and treatment approaches

    Ali Tahsin Güneş

    2013-03-01

    Full Text Available Angioedema (AE is defined as sudden, localized and transient swelling of the skin and/or mucous membranes. This swelling condition is a result of interstitial edema from vasoactive mediators increasing the permeability of postcapillary venules of the subcutaneous and submucosal tissues. When localized to the skin, it presents as asymmetric, nonpitting, nondependent, and occasionally painful edema. However, mucosal attacks, such as laryngeal edema and bowel involvement can produce severe discomfort and life-threatening symptoms. There are several forms including those involving dysfunction or depletion of the C1-inhibitor gene (classical hereditary AE types and acquired AE, allergic AE, drug-induced AE (nonsteroidal anti-inflammatory drug-induced AE, angiotensin converting enzyme inhibitor-induced AE, idiopathic and a recently described form, HAE type 3. These various forms of AE have overlapping symptoms, but some unique clinical and historical features as well as presence of accompanying urticaria can aid in the differential diagnosis. The key to successful management is to rule out conditions that masquerade as AE, detection and avoidance of triggers, early recognition of attacks, and aggressive airway management when warranted. In this article, common and rare forms as well as clinical symptoms, differential diagnosis, and treatment approaches for AE are reviewed.

  2. Amitriptyline and bromazepam in the treatment of vibratory angioedema: which role for neuroinflammation?

    Guarneri, Fabrizio; Guarneri, Claudio; Marini, Herbert Ryan

    2014-01-01

    Vibratory angioedema is a rare form of physical urticaria, hereditary or acquired, which occurs at body sites exposed to vibrations. Pathogenic mechanisms of disease are not completely clear and, consequently, current pharmacological treatment is sometimes unsatisfactory. We report the case of a horn player affected by acquired vibratory angioedema, relapsing after prolonged use of the instrument and resistant to systemic antihistamines and corticosteroids, which successfully responded to therapy with low doses of amitriptyline and bromazepam. A neuroinflammatory mechanism can be likely implicated in the pathogenesis of vibratory angioedema, in line with many different cutaneous/mucosal diseases involving a complex interplay of homeostatic/allostatic systems. Furthermore, in mucosal diseases, such as vibratory angioedema, physical/psychological stressors have a relevant role. In such cases, because of the complex interplay between nervous and immune system, the pharmacological activity of benzodiazepines and typical antidepressants may downregulate neuroinflammation. PMID:25052839

  3. Hereditary Neuropathies

    ... group of inherited disorders affecting the peripheral nervous system. The hereditary neuropathies are divided into four major subcategories: hereditary motor and sensory neuropathy, hereditary sensory neuropathy, hereditary motor neuropathy, and ...

  4. 'Epinephrine-resistant' angioedema.

    Ange, Nikhita; Rabbolini, David J; Pidcock, Michael; Randall, Katrina L

    2016-01-01

    A man in his 60s was brought to the emergency department, with airway compromise and dysarthria due to a grossly enlarged tongue. As he was on a current course of antibiotics, he was treated for a likely antibiotic-associated allergic reaction. However, as he failed to improve with intramuscular and nebulised epinephrine, another cause of his symptoms was sought. Further discussion revealed a history of chronic lymphocytic leukaemia (CLL), which had recently relapsed. Investigations were ordered to confirm that the symptoms were due to acquired angioedema, and the patient was managed for this diagnosis based on the presence of an undetectable C4 level. This diagnosis was later confirmed when the results of specialist tests became available. The patient was treated for his relapsed CLL with good effect, and has had no further episodes of angioedema and an improvement in the level of his C1 esterase protein level and function. PMID:26823364

  5. Life-threatening angioedema of the tongue: the detection of the RNA of B henselae in the saliva of a male patient and his dog as well as of the DNA of three Bartonella species in the blood of the patient.

    Lösch, Barbara; Wank, Rudolf

    2014-01-01

    Non-hereditary angioedema is a common disease with a prevalence between 5% and 19% and approximately half of the patients experience a swelling of the tongue. We report a case of a 49-year-old Caucasian man with a gross life-threatening angioedema of the tongue, whose attacks occurred every 4 weeks. The most frequent causes of angioedema were excluded. We detected DNA and RNA from Bartonella henselae in the blood and saliva of the patient and in the saliva of the patient's hunting dog. Treatment with azithromycin plus minocycline cleared the blood and saliva of RNA and DNA of Bartonella species, and the patient has been free from angioedema for 1 year. None of the therapy modalities used to treat the hereditary form or ACE or allergy-induced angioedema affect the detrimental course caused by Bartonella species. We therefore suggest that a molecular Bartonella test be included in the analysis of angioedema. PMID:24654245

  6. The Use of Plasma-Derived Complement C1-Esterase Inhibitor Concentrate (Berinert®) in the Treatment of Angiotensin Converting Enzyme-Inhibitor Related Angioedema

    Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette; Rasmussen, Eva Rye

    2016-01-01

    concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema......Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor...

  7. Acute parvovirus B19 infection in identical twins unmasking previously unidentified hereditary spherocytosis.

    Forde, Donall G; Cope, Alison; Stone, Ben

    2014-01-01

    Identical Caucasian male twins, previously fit, presented 1 week apart with short histories of fever and lethargy. The twins were febrile at presentation with profound pancytopaenia and evidence of haemolysis. There was no rash or arthralgia. Both required multiple red cell transfusions. The twins had positive IgM serology for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and parvovirus B19. EBV viral capsid antigen and Epstein-Barr nuclear antigen IgGs were also positive however, suggesting past EBV exposure. Parvovirus B19 DNA was detected from peripheral blood PCR; CMV and EBV DNA PCRs were negative. Convalescent serology demonstrated no evolution of the CMV serological response, that is no IgG to CMV developed which implies an initial non-specific polyclonal IgM response. The twins recovered fully over 7 days, the first with a course of prednisolone and the second spontaneously. They were diagnosed with hereditary spherocytosis on convalescent blood films. On further questioning, a family history of hereditary spherocytosis was eventually revealed. The twins' maternal grandmother was known to have the condition asymptomatically. Their mother had prior to this never been tested, but later bloods would reveal a compatible biochemical picture. PMID:25073523

  8. Recurrent gastrointestinal hemorrhage in treatment with dasatinib in a patient showing SMAD4 mutation with acute lymphoblastic leukemia Philadelphia positive and juvenile polyposis hereditary hemorrhagic telangiectasia syndrome

    Chiara Sartor

    2013-07-01

    Full Text Available We report a case of a patient affected by juvenile polyposis and hereditary hemorrhagic telangiectasia linked to a SMAD4 mutation who developed acute lymphoblastic leukemia positive for the Philadelphia chromosome translocation and with a complex karyotype. During the treatment with the tyrosine kinase inhibitor dasatinib the patient presented recurrent severe gastrointestinal hemorrhages linked to the genetic background and aggravated by thrombocytopenia.

  9. [Round Table: Urticaria and angioedema: introduction and classification].

    Alonso Lebrero, E

    1999-01-01

    Urticaria and angioedema are common diseases in children and adults. Approximately 15-25% of the population will have urticaria or angioedema at least once in their life-time. Urticaria is characterized as the appearance of erythematous, circumscribed, elevated, pruritic, edematous swelling of the upper dermal tissue. Erythematous swelling of the deeper cutaneous and subcutaneous tissue is called angioedema. In angioedema lesions are less pruritic but pain and burning are common. Urticaria may occur in any part of the body, whereas angioedema often involves face, extremities or genitalia. In contrast to other forms of edema there are not symmetric distribution. Urticaria and angioedema are often associated. Urticaria is considered acute if symptoms are present for less than 6 weeks, but usually in childhood lesions disappear in a few days. In chronic urticaria symptoms are longer than 6 weeks; if the episodes were of shorter duration than the symptoms-free periods urticaria is considered recurrent. Acute urticaria has been reported to be the common type in childhood and chronic urticaria is more frequent in adults. Acute urticaria is usually a self-limited benign disease in young children. Nevertheless it is an uncomfortable nuisance, interfering daily activities and sleep, and produces psychosocial impact in patients and parents (an altered self-image is always an alarming situation). Urticaria is a frequent cause of emergency room visit but few patients need to be admitted. Urticaria has long been believed to be an allergic disease but clinically it has rare been proved to be so. The basic mechanism involves the release of diverse vasoactive mediators that arise from the activation of cells or enzymatic pathways. Histamine is the best known of these substances, and elicits the classic triple response consisting of vasodilatation (erythema), increased vascular permeability (edema) and an axon reflex that increases reaction. In contrast to simple symptoms and easy

  10. Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia.

    Felix, C A; Nau, M M; Takahashi, T.; Mitsudomi, T.; Chiba, I.; Poplack, D G; Reaman, G H; Cole, D E; Letterio, J J; Whang-Peng, J

    1992-01-01

    The p53 gene was examined in primary lymphoblasts of 25 pediatric patients with acute lymphoblastic leukemia by the RNase protection assay and by single strand conformation polymorphism analysis in 23 of 25 cases. p53 mutations were found to occur, but at a low frequency (4 of 25). While all four mutations were identified by single strand conformation polymorphism, the comparative sensitivity of RNase protection was 50% (2 of 4). Heterozygosity was retained at mutated codons in 3 of 4 cases. ...

  11. Congenital anomalies, hereditary diseases of the pancreas, acute and chronic pancreatitis

    The most important congenital anomalies include pancreas divisum, annular pancreas and ectopic pancreas. Patients with pancreas divisum may be more susceptible to acute or chronic pancreatitis and patients with an annular pancreas may develop duodenal stenosis. In pancreas divisum the key finding is the visualization of the main duct draining into the duodenum via the small papilla, separated from the common bile duct. Annular pancreas may show as a well defined ring of pancreatic tissue that encircles the duodenum. Ectopic pancreas is usually asymptomatic but may give rise to abdominal complaints and may be confused with submucosal tumors. Acute pancreatitis is classified as mild or severe. In mild forms ultrasound is the imaging modality of choice whereas in severe forms with extensive pancreatic and peripancreatic necroses computed tomography is the favored method. It is crucial to identify signs and criteria that come along with an increased risk of infection of the necroses. MRI plays an inferior role in the assessment of acute pancreatitis. Chronic pancreatitis is a longstanding inflammatory and fibrosing process causing pain and loss of function. Cross-section imaging is particularly in demand for the detection of complications and the differentiation from pancreatic cancer. Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by lymphoplasmacytic infiltration and fibrosis, and favourable response to corticosteroid treatment. (orig.)

  12. Safety and Usage of C1-Inhibitor in Hereditary Angioedema

    Riedl, Marc A; Bygum, Anette; Lumry, William;

    2016-01-01

    ) and 16.6 IU/kg (prophylaxis). Approximately 95% of infusions were administered outside of a health care setting. No adverse events (AEs) were reported in retrospective data. Among prospective data (n = 296 subjects; 9148 infusions), 252 AEs were reported in 85 (28.7%) subjects (rate of 0.03 events....../infusion); 9 events were considered related to pnfC1-INH. Two thromboembolic events were reported in subjects with thrombotic risk factors. No patient was noted to have undergone viral testing for suspected blood-borne infection during registry participation. CONCLUSIONS: The findings from this large......, international patient registry documented widespread implementation of pnfC1-INH self-administration outside of a health care setting consistent with current HAE guidelines. These real-world data revealed pnfC1-INH usage for a variety of reasons in patients with HAE and showed a high level of safety regardless...

  13. Clinical and Laboratory Characteristics That Differentiate Hereditary Angioedema in 72 Patients with Angioedema

    Isao Ohsawa

    2014-01-01

    Conclusions: Early onset of AE, positive family history, recurrent AE in the extremities and GI tract, and suffocation are distinctive characteristics of HAE. A low serum level of C4 is a useful marker for making a differential diagnosis of HAE.

  14. New PRSS1 and common CFTR mutations in a child with acute recurrent pancreatitis, could be considered an "Hereditary" form of pancreatitis ?

    Galli Elena

    2010-10-01

    Full Text Available Abstract Background acute recurrent pancreatitis is a complex multigenic disease, the diagnosis is even more difficult when this disease develops in a child. Case Presentation a 6-years old boy, hospitalized with epigastric pain radiating to the back showed high serum levels of serum amylase, lipase, CRP and erythrosedimentation rate. Several similar milder episodes of pain, followed by quick recovery and complete disappearance of symptoms were reported during the previous 13 months. The child was medically treated and after 7 days with normal clinic and laboratory tests was discharged with a hypolipidic diet. All the known aetiologic hypotheses were excluded by anamnestic investigation, clinical observation and biochemical evaluation, whereas, anatomic abnormality were excluded by a secretin stimulated magnetic resonance (MRI. At the last follow-up visit, (11 months later, the child showed a normal body weight and anthropometric profile, without further abdominal pain. Mutation screening for coding regions of PRSS1, SPINK1, CFTR and the new hereditary pancreatitis-associated chymotrypsin C (CTRC genes showed a novel variation, c.541A > G (p.S181G, in the exon 4 of PRSS1 gene and the classical CF p.F508del mutation in the CFTR. Both mutations were present in his clinically normal mother and absent in the patient's father. Conclusions this report extend the spectrum of PRSS1 mutations, however, the absence of family history of pancreatitis leaves the present case without the hallmark of the hereditary origin of pancreatitis. At the present knowledge it can be only stated that the combined genotype CFTR (F508del/PRSS1 (S181G is associated to a mild phenotype of acute recurrent pancreatitis in this child without any further conclusion on its pathogenetic role or prediction on the course of the disease.

  15. Angioedema-Urticaria Due to Acitretin.

    Solak, Berna; Metin, Nurcan; Erdem, Mustafa Teoman

    2016-01-01

    Acitretin is a synthetic oral retinoid that has been used for a number of dermatological diseases. Several side effects of acitretin have been reported such as teratogenicity, cheilitis, xerosis, dyslipidemia, and photosensitivity. Many drugs, mainly antibiotics and nonsteroidal anti-inflammatory drugs, can cause angioedema-urticaria. We present the case of angioedema-urticaria due to acitretin, confirmed by oral provocation test, in a 61-year-old man with psoriasis. To the best of our knowledge, only 1 case of angioedema due to oral acitretin has been reported in the literature so far. We report this case to draw attention that acitretin may cause angioedema-urticaria and to inform patients about this risk besides other side effects due to acitretin. PMID:26820109

  16. The Use of Plasma-Derived Complement C1-Esterase Inhibitor Concentrate (Berinert®) in the Treatment of Angiotensin Converting Enzyme-Inhibitor Related Angioedema

    Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette; Rasmussen, Eva Rye

    2016-01-01

    Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema (ACEi-AE) of the hypopharynx that completely resolved rapidly after the infusion of plasma-derived C1-inhibitor concentrate adding to the sparse reports in the existing literature. PMID:27123347

  17. The Use of Plasma-Derived Complement C1-Esterase Inhibitor Concentrate (Berinert®) in the Treatment of Angiotensin Converting Enzyme-Inhibitor Related Angioedema.

    Hermanrud, Thorbjørn; Duus, Nicolaj; Bygum, Anette; Rasmussen, Eva Rye

    2016-01-01

    Angioedema of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to pharmaceuticals influencing the generation or degradation of the vasoactive molecule bradykinin. Plasma-derived C1-esterase inhibitor concentrate is a well-established treatment option of hereditary and acquired complement C1-esterase inhibitor deficiency, which are also mediated by an increased level of bradykinin resulting in recurrent angioedema. We here present a case of severe angiotensin converting enzyme-inhibitor related angioedema (ACEi-AE) of the hypopharynx that completely resolved rapidly after the infusion of plasma-derived C1-inhibitor concentrate adding to the sparse reports in the existing literature. PMID:27123347

  18. Cytokine-associated angioedema syndromes including episodic angioedema with eosinophilia (Gleich's Syndrome).

    Banerji, Aleena; Weller, Peter F; Sheikh, Javed

    2006-11-01

    Angioedema can be associated with many disorders and the presentation can be variable. Subsets of the angioedema syndromes are thought to be cytokine mediated (Table 1). Of these, the best described are the episodic angioedema with eosinophilia syndrome (Gleich's syndrome) and non-episodic angioedema with eosinophilia, which share some common features, but appear to have differences in pathophysiology. NERDS (nodules, eosinophilia, rheumatism, dermatitis and swelling), Clarkson syndrome (idiopathic capillary leak syndrome), and angioedema associated with aldesleukin (human recombinant IL-2) and IFN-alpha have also been reported in the literature, and have been discussed in this review. There is still much to be learned about the pathophysiology, diagnosis, and treatment of patients with these disorders. Our hope is that this review will be of help to those readers who care for patients with these disorders, and will stimulate interest in further research into the pathophysiology of these conditions. PMID:17085290

  19. The Janus faces of acquired angioedema: C1-inhibitor deficiency, lymphoproliferation and autoimmunity.

    Wu, Maddalena Alessandra; Castelli, Roberto

    2016-02-01

    Several clinical and biological features of lymphoproliferative diseases have been associated with an increased risk of developing autoimmune manifestations. Acquired deficiency of C1-inhibitor (C1-INH) (AAE) is a rare syndrome clinically similar to hereditary angioedema (HAE) characterized by local increase in vascular permeability (angioedema) of the skin and the gastrointestinal and oro-pharyngo-laryngeal mucosa. Bradykinin, a potent vasoactive peptide, released from high molecular weight kininogen when it is cleaved by plasma kallikrein (a serine protease controlled by C1-INH), is the mediator of symptoms. In total 46% of AAE patients carry an underlying hematological disorder including monoclonal gammopathy of uncertain significance (MGUS) or B cell malignancies. However, 74% of AAE patients have anti-C1-INH autoantibodies without hematological, clinical or instrumental evidence of lymphoproliferative disease. Unlike HAE patients, AAE patients usually have late-onset symptoms, do not have a family history of angioedema and present variable response to treatment due to the hypercatabolism of C1-INH. Experiments show that C1-INH and/or the classical complement pathway were consumed by the neoplastic lymphatic tissues and/or anti-C1-INH neutralizing autoantibodies. Therapy of AAE follows two directions: 1) prevention/reversal of the symptoms of angioedema; and 2) treatment of the associated disease. Different forms of B cell disorders coexist and/or evolve into each other in AAE and seem to be dominated by an altered control of B cell proliferation, thus AAE represents an example of the strict link between autoimmunity and lymphoproliferation. PMID:26068904

  20. Hereditary hemochromatosis

    To describe the clinical and laboratory features of hereditary hemochromatosis associated liver disease in a tertiary care hospital. Study Design: Observational study. Place and Duration of Study: The Aga Khan University Hospital, Karachi, from January 2002 to October 2012. Methodology: Charts of patients with Hereditary Hemochromatosis (HHC) were reviewed. Data collected and analyzed consisting of clinical presentations, liver function tests, serum ferritin, transferrin saturation, hepatic imaging and histology in patients with HHC. Results: A total of 22 patients were identified as having hemochromatosis. All subjects were men with a mean age of 53 ± 9.2 years at the time of diagnosis. The most common presentation was skin pigmentation seen in 17 (77%), followed by loss of libido/ impotence in 11 (50%) and then arthralgias in 10 (45%) and weakness in 6 (27%). Eleven (50%) subjects had diabetes mellitus and one subject had concomitant cardiac involvement. Patients with diabetes were diagnosed earlier as compared to those without it. Eighteen (81%) subjects had cirrhosis at the time of diagnosis. Serum iron was 164 ± 53 ug/dl, ferritin 3391 ± 1960 ug/L, TIBC 202 ± 61 ug/dl and transferrin saturation 76.8 ± 14%. Liver biopsy was done in 10 (45%) and using Pearls stain histopathological features were consistent with hemochromatosis and none had carcinoma. Only 3 (14%) patients had regular phlebotomy. Conclusion: Hemochromatosis is not a rare disease in Pakistan and should be looked in those subjects whose liver function tests are deranged. (author)

  1. Congenital anomalies, hereditary diseases of the pancreas, acute and chronic pancreatitis; Entwicklungsstoerungen, angeborene Erkrankungen des Pankreas, akute und chronische Pankreatitis

    Brambs, Hans-Juergen; Juchems, Markus [Universitaetsklinikum Ulm (Germany). Abt. fuer Diagnostische und Interventionelle Radiologie

    2011-06-15

    The most important congenital anomalies include pancreas divisum, annular pancreas and ectopic pancreas. Patients with pancreas divisum may be more susceptible to acute or chronic pancreatitis and patients with an annular pancreas may develop duodenal stenosis. In pancreas divisum the key finding is the visualization of the main duct draining into the duodenum via the small papilla, separated from the common bile duct. Annular pancreas may show as a well defined ring of pancreatic tissue that encircles the duodenum. Ectopic pancreas is usually asymptomatic but may give rise to abdominal complaints and may be confused with submucosal tumors. Acute pancreatitis is classified as mild or severe. In mild forms ultrasound is the imaging modality of choice whereas in severe forms with extensive pancreatic and peripancreatic necroses computed tomography is the favored method. It is crucial to identify signs and criteria that come along with an increased risk of infection of the necroses. MRI plays an inferior role in the assessment of acute pancreatitis. Chronic pancreatitis is a longstanding inflammatory and fibrosing process causing pain and loss of function. Cross-section imaging is particularly in demand for the detection of complications and the differentiation from pancreatic cancer. Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by lymphoplasmacytic infiltration and fibrosis, and favourable response to corticosteroid treatment. (orig.)

  2. Leber Hereditary Optic Neuropathy

    Kopishinskaya S.V.

    2014-06-01

    Full Text Available Leber optic neuropathy is mitochondrial neurodegenerative disease manifested by progressive visual deterioration due to optic nerve atrophy. It is most frequently manifested in young people aged from 18 to 30, male patients prevailing. The disease is characterized by maternal inheritance, and the inheritance of a feature discontinues in men. In 95% cases Leber hereditary optic neuropathology is due to one of three known mitochondrial DNA mutations, its type being important in relation to the disease prognosis. The disease course has a number of succeeding stages: preclinical, acute and chronic (atrophic. The disease diagnosis is based on the characteristic clinical presentation of sequential impairment of both eyes forming central scotoma, the analysis of family history and detection of specific mutations. The present clinical observation illustrates the difficulties in Leber disease diagnosis.

  3. Is Pancreatic Cancer Hereditary?

    ... Board Patient Education / Basics of Pancreatic Cancer Is pancreatic cancer hereditary? Cancer of the pancreas is a genetic ... found in cigarette smoke. The genetics of hereditary pancreatic cancer is a focus of research at Johns Hopkins. ...

  4. Hereditary Spastic Paraplegia

    ... there any treatment? What is the prognosis? What research is being done? Clinical Trials Organizations What is Hereditary Spastic Paraplegia? Hereditary spastic paraplegia (HSP), also called familial spastic paraparesis (FSP), refers to a group of inherited disorders that ...

  5. Hereditary Hemorrhagic Telangiectasia - HHT

    ... access catheters Vertebroplasty Women and vascular disease Women's health Social Media Facebook Twitter ... Hereditary Hemorrhagic Telangiectasia - HHT Interventional Radiologists Offer Non-surgical Treatment for Underdiagnosed Genetic Disorder ...

  6. How Not to Be Misled by Disorders Mimicking Angioedema

    Andersen, Michelle Fog; Longhurst, Hilary J; Rasmussen, Eva Rye;

    2016-01-01

    BACKGROUND: Angioedema is a vascular reaction involving the lower dermis, subcutis and/or submucosal tissue and causing a temporary localized swelling in any part of the body. For many health care professionals, the diagnosis presents an ongoing challenge; several disorders may manifest with...... subcutaneous or submucosal swelling and falsely be assumed to be angioedema. The clinicians at the emergency department and in the immunology/allergy clinics must be skilled at recognizing the features of angioedema and its differential diagnosis. METHODS: The review is based on a literature search with...... specific indexing terms in PubMed, a review of bibliographies and the authors' clinical experience. RESULTS: The most essential diseases that mimic angioedema, the so-called pseudoangioedemas, will each be discussed and illustrated by clinical photos, pointing out key features that help clarify the...

  7. Visceral Angioedema Induced by Angiotensin Converting Enzyme Inhibitor: Case Report

    Beatriz Frutuoso

    2016-05-01

    Conclusion: The diagnosis of intestinal angioedema induced by angiotensin converting enzyme inhibitor can be challenging and time consuming due to its rarity and nonspecific symptoms, which may lead to underdiagnosis of this entity.

  8. ACE-I Angioedema: Accurate Clinical Diagnosis May Prevent Epinephrine-Induced Harm

    R. Mason Curtis; Sarah Felder; Rozita Borici-Mazi; Ian Ball

    2016-01-01

    Introduction: Upper airway angioedema is a life-threatening emergency department (ED) presentation with increasing incidence. Angiotensin-converting enzyme inhibitor induced angioedema (AAE) is a non-mast cell mediated etiology of angioedema. Accurate diagnosis by clinical examination can optimize patient management and reduce morbidity from inappropriate treatment with epinephrine. The aim of this study is to describe the incidence of angioedema subtypes and the management of AAE. We evaluat...

  9. Pathophysiology, clinical manifestation and management of angioedema - our experience

    Aleksić Aleksandra

    2015-01-01

    Full Text Available Introduction. Angioedema is characterized by subcutaneous and/or submucosal swelling usually localized to the lips, eyelids, tongue, oral cavity, larynx and pharynx. Various types of angioedema, caused by different pathophysiologic mechanisms, can have the same or very similar clinical picture and require different diagnostic and therapeutic procedures. The immediate threat to life as a result of rapidly developed edema of the pharynx and larynx with airway obstruction requires endotracheal intubation or emergency tracheotomy. Standard therapy, which includes epinephrine, second-generation antihistamines and steroids, is not effective in the treatment of all types of angioedema. Objective. On the basis of the clinical presentation and course of angioedema, this retrospective study was aimed at contributing to a better understanding of the etiopathogenesis of the disease and at helping determine the most effective available treatment modalities. Methods. This retrospective study included patients treated under the diagnosis of angioedema of the upper aerodigestive tract between 2000 and 2012 in the Department of Otorhinolaryngology, Clinical Center of Banja Luka. Results. A total of 76 subjects were included in the study. The average age was 62.8 years. There were 40 (52.6% male and 36 (47.4% female patients. The largest number of patients (44.7% had type II angioedema. Almost half of the patients or 36 patients (47.4% were on treatment with an angiotensinconverting enzyme inhibitor (ACEi, but there was no statistically significant difference under the total number of patients (p=0.678. Conclusion. Better understanding of pathophysiologic mechanisms and the adoption of diagnostic protocols contributes to more effective treatment of angioedema.

  10. Learning about Hereditary Hemochromatosis

    ... and Its Implications Meeting A 1997 ELSI Report Learning About Hereditary Hemochromatosis What do we know about ... and treatment information. Hosted by the Dolan DNA Learning Center at Cold Spring Harbor Laboratory. Iron Overload ...

  11. [Hereditary angioneurotic edema in children].

    Farkas, H; Harmat, G; Füst, G; Varga, L; Visy, B

    2000-11-19

    Hereditary angioneurotic edema results from the deficiency of C1-esterase inhibitor. The clinical picture of this autosomal dominant disorder is characterized by recurrent attacks of edema formation in the subcutis and/or the submucosa. The clinical records of 21 children with established hereditary angioneurotic edema were reviewed. Follow-up care included laboratory check-ups and abdominal ultrasound. Clinical manifestations of the disease first occurred in 2.5 to 12 years of age. Mechanical trauma was the most common precipitating factor. Pedigree-analysis revealed 19 patients with afflicted relatives. Long-term prophylaxis was initiated with tranexamic acid and danazol in 10 cases; 2 children required short-term prophylaxis. Therapy improved serum complement parameters significantly and reduced the frequency and severity of clinical manifestations. Acute, life-threatening edematous attacks were treated by the administration of C1-inhibitor concentrate, which achieved the resolution of the edema within several hours. Abdominal ultrasonography performed during the attack invariably demonstrated transitory ascites that resolved spontaneously after treatment. Adequate prophylaxis and follow-up care can spare pediatric patients from edematous attacks. Undesirable adverse effects can be avoided and the patient's quality of life can be enhanced considerably by administering the lowest effective drug dose. PMID:11143287

  12. Angiotensin Converting Enzyme-induced Angioedema - A Dangerous New Epidemic

    Rasmussen, Eva Rye; Mey, Kristianna; Bygum, Anette

    2013-01-01

    Angioedema is a sudden localised and often asymmetric swelling of the skin or mucous membranes caused by transient increased endothelial permeability causing plasma extravasation. In the last decades the incidence of severe angioedema involving the upper airways and even fatal outcome due to...... asphyxia has increased. This is mainly due to pharmaceuticals such as angiotensin converting enzyme-inhibitors, which are extensively used worldwide. Some aspects of the pathophysiology have been elucidated and the vasoactive molecule bradykinin is shown to be one of the main causative agents. The...

  13. Aniseed-induced nocturnal tongue angioedema.

    Gázquez García, V; Gaig Jané, P; Bartolomé Zavala, B

    2007-01-01

    Aniseed is a spice native to the eastern Mediterranean region. Cases of simultaneous hypersensitivity to celery, mugwort pollen, and spices of the Umbelliferae family have been described as the celery-mugwort-spices syndrome. We report a case of aniseed-induced tongue angioedema. Skin prick tests to foods proved positive only to aniseed. Serum-specific immunoglobulin (Ig) E determination by enzyme allergosorbent test was 0.4 kU/L to aniseed extract and 0.6 kU/L to tare and cumin seeds. The molecular mass of the IgE-binding proteins studied by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) immunoblotting revealed a broad IgE-binding band of 12.9-13.7 kd in aniseed and tare extract assays and a broad band of 15-17.5 kd in cumin extract. This is the first case of type I hypersensitivity due to aniseed liqueur ingestion reported. SDS-PAGE immunoblotting study showed a broad specific IgE-binding band of 12.9-13.7 kd when aniseed extract was incubated with the patient's serum; this band might correspond to the protein responsible for the described symptoms. PMID:18088024

  14. A novel assay to diagnose hereditary angioedema utilizing inhibition of bradykinin-forming enzymes

    Joseph, Kusumam; Bains, Sonia; Tholanikunnel, Baby G;

    2015-01-01

    . This was evident regardless whether we measured factor XIIa-C1-INH or kallikrein-C1-INH complexes, and the two assays were in close agreement. By contrast, testing the same samples utilizing the commercial method (complex ELISA, Quidel Corp.) revealed levels of C1-INH between 0 and 57% of normal (mean, 38%) and 42...

  15. Psychometric Field Study of Hereditary Angioedema Quality of Life Questionnaire for Adults

    Prior, Nieves; Remor, Eduardo; Pérez-Fernández, Elia;

    2016-01-01

    social functioning, concern about offspring, perceived control over illness, and mental health). Strong psychometric properties were observed (Cronbach's α 0.92; test-retest reliability 0.87). Convergent validity showed mild to moderate correlations with SF-36v2 physical and mental component summaries (0...... version of the HAE-QoL was pilot tested in 332 patients, and accurate data were obtained from 290 patients from 11 countries. The reduction process resulted in a new version with 25 items and 7 dimensions (treatment difficulties, physical functioning and health, disease-related stigma, emotional role and...

  16. Activation of the ficolin-lectin pathway during attacks of hereditary angioedema

    Csuka, Dorottya; Munthe-Fog, Lea; Hein, Estrid;

    2014-01-01

    enrolled. We analyzed blood samples drawn during attacks, and obtained 35 samples from the same patients during symptom-free periods. The serum levels of ficolin-2, ficolin-3, MASP-2, ficolin-3/MASP-2 complex, C1-INH, and C4, as well as the extent of ficolin-3-mediated terminal complement complex (FCN3-TCC......) deposition, were measured using ELISA-based methods. RESULTS: Levels of MASP-2 and of the ficolin-3/MASP-2 complex were elevated (P < .0001 and .033, respectively), whereas that of FCN3-TCC was lower (P < .0001) during attacks than during the symptom-free period. During symptom-free periods, FCN3-TCC...

  17. Hereditary Pancreatic and Hepatobiliary Cancers

    Ashraf Haddad; Kowdley, Gopal C; Timothy M. Pawlik; Cunningham, Steven C.

    2011-01-01

    Hereditary etiologies of pancreatic and hepatobiliary cancers are increasingly recognized. An estimated >10% of pancreatic and increasing number of hepatobiliary cancers are hereditary. The cumulative risk of hereditary pancreatic cancer ranges from measurable but negligible in cystic fibrosis to a sobering 70% in cases of hereditary pancreatitis. Candidates for pancreatic cancer surveillance are those with a risk pancreatic cancer estimated to be >10-fold that of the normal population. Scree...

  18. Angioedema-like allergic contact dermatitis related to black henna

    Gokalp, Hilal; Kaya, Kismet

    2014-01-01

    Allergic contact dermatitis related to para-phenylendiamine (PPD) from temporary black henna tattoos and hair dyes has become an epidemic in recent years. Several cases of adverse skin reactions to PPD have been reported in the literature. Herein, we present a case of angioedema-like allergic contact dermatitis related to hair coloring with henna.

  19. Angioedema in a Patient with C1 Esterase Inhibitor Deficiency

    Antonino Murinello

    2005-09-01

    A case of atypical acquired angioedema in a 49-year old man, responding favourably to cinnarizine and alcohol abstinence, is presented in this article. Cinnarizine was prescribed due to presumed alcoholic liver disease. The clinical significant amelioration was not associated with concomitant good laboratory result, which is a relatively common occurrence.

  20. Hereditary and metabolic myelopathies.

    Hedera, Peter

    2016-01-01

    Hereditary and metabolic myelopathies are a heterogeneous group of neurologic disorders characterized by clinical signs suggesting spinal cord dysfunction. Spastic weakness, limb ataxia without additional cerebellar signs, impaired vibration, and positional sensation are hallmark phenotypic features of these disorders. Hereditary, and to some extent, metabolic myelopathies are now recognized as more widespread systemic processes with axonal loss and demyelination. However, the concept of predominantly spinal cord disorders remains clinically helpful to differentiate these disorders from other neurodegenerative conditions. Furthermore, metabolic myelopathies are potentially treatable and an earlier diagnosis increases the likelihood of a good clinical recovery. This chapter reviews major types of degenerative myelopathies, hereditary spastic paraplegia, motor neuron disorders, spastic ataxias, and metabolic disorders, including leukodystrophies and nutritionally induced myelopathies, such as vitamin B12, E, and copper deficiencies. Neuroimaging studies usually detect a nonspecific spinal cord atrophy or demyelination of the corticospinal tracts and dorsal columns. Brain imaging can be also helpful in myelopathies caused by generalized neurodegeneration. Given the nonspecific nature of neuroimaging findings, we also review metabolic or genetic assays needed for the specific diagnosis of hereditary and metabolic myelopathies. PMID:27430441

  1. Hereditary Hearing Loss.

    Tran, LenhAnh P.; Grundfast, Kenneth M.

    1997-01-01

    This article discusses inheritance patterns in hearing loss, epidemiology, clues to genetic causes, locating genes that cause hereditary disorders, genes related to hearing loss disorders in individuals with Usher syndrome, Waardenburg syndrome, Treacher-Collins syndrome, Branchio-oto-renal and Pendred syndromes, and the significance of finding…

  2. [Hereditary transthyretin amyloidosis].

    Hund, E

    2014-10-01

    Hereditary amyloidosis is an autosomal dominant fatal multisystem disease caused by extracellular deposition of misfolded proteins and, therefore represents a hereditary protein folding or deposition disease that leads to progressive organ damage and eventually death. In most instances mutations within the transthyretin gene are the underlying cause. The main manifestation is a rapidly progressing axonal sensorimotor and autonomic polyneuropathy (familial amyloid polyneuropathy, FAP). Cardiac involvement is frequent in FAP and additional manifestations include the gastrointestinal tract and the eyes. A second manifestation type is cardiomyopathy with little or no polyneuropathy (familial amyloid cardiomyopathy, FAC). For therapy, orthotopic liver transplantation has been established for 25 years. Recently, the oral agent tafamidis, a transthyretin stabilizer, was licensed for treatment of stage 1 polyneuropathy. Additional treatment options are currently being studied. PMID:25123367

  3. Hereditary breast cancer

    Larsen, Martin J; Thomassen, Mads; Gerdes, Anne-Marie;

    2014-01-01

    Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight into the t......Pathogenic mutations in BRCA1 or BRCA2 are only detected in 25% of families with a strong history of breast cancer, though hereditary factors are expected to be involved in the remaining families with no recognized mutation. Molecular characterization is expected to provide new insight...... into the tumor biology to guide the search of new high-risk alleles and provide better classification of the growing number of BRCA1/2 variants of unknown significance (VUS). In this review, we provide an overview of hereditary breast cancer, its genetic background, and clinical implications, before focusing...... on the pathologically and molecular features associated with the disease. Recent transcriptome and genome profiling studies of tumor series from BRCA1/2 mutation carriers as well as familial non-BRCA1/2 will be discussed. Special attention is paid to its association with molecular breast cancer subtypes as well...

  4. Medical management of hereditary optic neuropathies

    ChiaraLa Morgia

    2014-07-01

    Full Text Available Hereditary optic neuropathies are diseases of the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e. the maternally inherited Leber’s Hereditary Optic Neuropathy (LHON and Dominant Optic Atrophy (DOA. They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1 and 14484/ND6 for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone. Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising venue that still needs to be validated.

  5. Genetics Home Reference: hereditary fructose intolerance

    ... Genetics Home Health Conditions hereditary fructose intolerance hereditary fructose intolerance Enable Javascript to view the expand/collapse ... Print All Open All Close All Description Hereditary fructose intolerance is a condition that affects a person's ...

  6. Visceral Angioedema Induced by Angiotensin Converting Enzyme Inhibitor: Case Report

    Beatriz Frutuoso; Joana Esteves; Mafalda Silva; Pedro Gil; Ana Cristina Carneiro; Sílvio Vale

    2016-01-01

    Introduction: Intestinal angioedema is a rare adverse effect of angiotensin converting enzyme inhibitors. Clinical case: A 42-year old woman presented to the Emergency Department complaining of diffuse abdominal pain, predominantly in the right quadrants, with no other associated symptoms. She had been started on perindopril plus indapamide 72 h before the admission for arterial hypertension. There was no other relevant background. Physical examination suggested peritoneal irritation...

  7. Transient small bowel angioedema due to intravenous iodinated contrast media

    Hu, Xiu-Hua; Gong, Xiang-Yang; Hu, Peng

    2012-01-01

    Three cases of transient proximal small bowel angioedema induced by intravenous administration of nonionic iodinated contrast media (CM) are presented. Computed tomography (CT) images in the venous phase displayed the proximal small bowel with circumferential thickening of the wall including the duodenum and proximal segment of the jejunum. The bowel wall was normal in non-enhanced images, and normal or inconspicuous in arterial phase enhanced images. In one of the three cases, the bowel wall...

  8. Pharmacogenetics of ACE inhibitor-induced angioedema and cough : a systematic review and meta-analysis

    Mahmoudpour, Seyed Hamidreza; Leusink, Maarten; van der Putten, Lisa; Terreehorst, Ingrid; Asselbergs, Folkert W.; de Boer, Anthonius; Maitland-van der Zee, Anke H.

    2013-01-01

    Aim: Angioedema and cough are the two most important adverse effects of ACE inhibitors (ACEIs). Evidence exists that ACEI-related angioedema/cough is partly genetically determined and several genes have been identified to play a role in the development of ACEI-related adverse effects. Materials & me

  9. Hereditary Predispositions to Myelodysplastic Syndrome

    Sarah A. Bannon

    2016-05-01

    Full Text Available Myelodysplastic syndromes (MDS are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA, dyskeratosis congenita (DC, Diamond–Blackfan anemia (DBA, and Shwachman–Diamond syndrome (SBS, hallmarked by clinically-recognizable phenotypes (e.g., radial ray anomalies in FA and significantly increased risks for MDS and/or acute myeloid leukemia (AML in the setting of bone marrow failure. However, additional families with multiple cases of MDS or AML have long been reported in the medical literature with little known regarding potential hereditary etiologies. Over the last decade, genomic investigation of such families has revealed multiple genes conferring inherited risks for MDS and/or AML as the primary malignancy, including RUNX1, ANKRD26, DDX41, ETV6, GATA2, and SRP72. As these syndromes are increasingly appreciated in even apparently de novo presentations of MDS, it is important for hematologists/oncologists to become familiar with these newly-described syndromes. Herein, we provide a review of familial MDS syndromes and practical aspects of management in patients with predisposition syndromes.

  10. Hereditary Hemorrhagic Telangiectasia.

    Parambil, Joseph G

    2016-09-01

    Hereditary hemorrhagic telangiectasia (HHT) is an underrecognized and underdiagnosed autosomal-dominant angiodysplasia that has an estimated prevalence of 1 in 5000 individuals, with variable clinical presentations even within family members with identical mutations. The most common manifestations are telangiectasias of the skin and nasal mucosa. However, HHT can often be complicated by the presence of arteriovenous malformations and telangiectasias in the lungs, brain, gastrointestinal tract, and liver that are often silent and can lead to life-threatening complications of stroke and hemorrhage. This article reviews HHT for the pulmonologist, who is not uncommonly the first practitioner to encounter these patients. PMID:27514597