Medical Literature - 2007

Varga L, Biro A, Szeplaki G, Toth L, Horvath A, Fust G, et al 11/2007 Journal of Cellular & Molecular Medicine

Hereditary angioedema (HAE) is a rare disorder caused by the deficiency of the C1-inhibitor gene (C1INH) and characterized by recurrent bouts of angioedema. Autoimmune disorders frequently occur in HAE. Previously we found, that danazol has an adverse effect on serum lipid profile: reduced high-density lipoprotein (HDL) and elevated low-density lipoprotein (LDL) cholesterol levels are associated with long-term prophylactic use, whereas total cholesterol levels are unchanged. Our aim was to study the anti-cholesterol antibody (ACHA) production in HAE patients and compare it with those of healthy blood donors, and to investigate the possible associations between ACHA levels and serum lipid profile alterations caused by danazol. Anti-cholesterol IgG levels were measured by ELISA and their correlation with serum concentrations of total cholesterol, HDL, LDL, triglycerides was determined in HAE patients receiving/not receiving danazol. Serum ACHA levels were significantly higher in HAE patients, compared to healthy blood donors (P<0.0001). Longterm danazol prophylaxis had no effect on serum ACHA levels in HAE patients. However, we found a significant, negative correlation between ACHA levels and serum total cholesterol (r=-0.4033, P=0.0200), LDL (r=-0.4565, P=0.0076) and triglyceride (r=-0.4230, P=0.0121) levels only in danazol-treated patients, but not in HAE patients who did not receive long-term prophylaxis. Patients with HAE have higher baseline ACHA levels compared to healthy subjects, and this might reflect polyclonal B-cell activation. The latter would be a potential explanation for the lack of an increased incidence of infectious diseases in HAE patients, but might lead to increased autoimmunity.

Nov-Dec;11(6):1377-1383

Available online at: onlinelibrary.wiley.com/doi/10.1111/j.1582-4934.2007.00124.x/full

Longhurst HJ, Carr S, Khair K 1/2007 Clinical & Experimental Immunology

Economic and political factors have led to the increased use of home therapy programmes for patients who have traditionally been treated in hospital. Many patients with hereditary angioedema (HAE) experience intermittent severe attacks that affect their quality of life and may be life-threatening. These attacks are treated with C1-inhibitor concentrate which, for most patients, is infused at the local hospital. Home therapy programmes for HAE are currently being established. This paper reviews the extent of use of these programmes and summarizes the advantages and potential disadvantages of the concept so far. [References: 56].

Jan;147(1):11-17

Available online at: ncbi.nlm.nih.gov/pmc/articles/PMC1804208/

Lock RJ, Gompels MM 7/2007 Current Allergy & Asthma Reports

Hereditary angioedema, an autosomal dominant disorder, presents clinically as recurrent episodes of swelling. It results from either deficient production or function of C1 inhibitor. Acquired angioedema is associated with lymphoproliferative or autoimmune disease. Conventionally attenuated androgens and antifibrinolytics have been used for prophylaxis, both for the long term and presurgically. Fresh frozen plasma and plasma-derived C1 inhibitor concentrate have been used primarily for treatment of acute attacks. All have drawbacks in side effects or potential for infection transmission. New treatments (recombinant C1 inhibitor, icatibant, DX-88, and for acquired angioedema, rituximab) so far show good safety profiles. Early data suggest these may be effective treatment alternatives. The efficacy of current treatment and the potential held by newer agents that target specific elements in complement or kinin pathways are examined. Some agents are likely to have a wider role in treatment of other, more common, forms of angioedema. [References: 52].

Jul;7(4):264-269

Available online at: link.springer.com/article/10.1007/s11882-007-0039-6 (small fee)

Schneider L, Lumry W, Vegh A, Williams AH, Schmalbach T 8/2007 Journal of Allergy & Clinical Immunology

BACKGROUND: Hereditary angioedema (HAE) is a rare, autosomal-dominant disorder caused by C1 inhibitor gene mutation. Patients with HAE experience intermittent attacks of edema affecting the oropharynx, abdomen, gastrointestinal tract, and limbs. C1 inhibitor is the primary endogenous inhibitor of the kallikrein-kinin (contact) cascade. Unregulated kallikrein activation generates bradykinin, the likely mediator of the swelling and pain characterizing HAE attacks. Ecallantide, a novel, recombinant protein, potently inhibits kallikrein. This is the first placebo-controlled assessment in human beings of a therapeutic intervention to improve symptoms of HAE attacks under the hypothesis that the contact cascade is the putative pathway responsible for HAE pathology.

OBJECTIVE: To determine the safety and efficacy of ecallantide in patients with HAE. METHODS: This double-blind, placebo-controlled, ascending-dose study assessed efficacy and tolerability of ecallantide (5, 10, 20, or 40 mg/m(2) intravenously) in individuals experiencing acute HAE attacks (N = 49). Twelve patients were assigned to each dose level: 10 to ecallantide and 2 to placebo, per cohort.

RESULTS: Ecallantide treatment ameliorated the symptoms of HAE attacks: 72.5% (29/40) of patients treated with ecallantide versus 25.0% (2/8) of placebo patients reported significant improvement in symptoms within 4 hours (P = .0169). Ecallantide was well tolerated at all doses.

CONCLUSION: Ecallantide, a potent, specific inhibitor of plasma kallikrein, significantly improved HAE symptoms over placebo. The trial provides strong support for the role of the kallikrein-kinin cascade and its end product, bradykinin, in the pathophysiology of HAE. Further clinical trials are underway.

CLINICAL IMPLICATIONS: Ecallantide is a promising new therapy for HAE attacks.

Aug;120(2):416-422

Available online at: jacionline.org/article/S0091-6749%2807%2900864-0/fulltext

Prematta M, Gibbs JG, Pratt EL, Stoughton TR, Craig TJ 4/2007 Annals of Allergy, Asthma, & Immunology

BACKGROUND: Fresh frozen plasma (FFP) has been used as a treatment option for patients with hereditary angioedema (HAE) because it contains Cl esterase inhibitor, and alternate therapies are not yet available in the United States. However, because FFP also contains other substrates, it has been hypothesized to have the potential to worsen or precipitate an acute attack of HAE.

OBJECTIVE: To research patient records and the medical literature to determine whether FFP can exacerbate symptoms or precipitate an attack of HAE.

METHODS: The following keywords were searched in PubMed and OVID: hereditary angioedema, angioedema and fresh frozen plasma, angioedema and FFP, and hereditary angioneurotic edema. English-language articles were searched from 1966 to the present. Also, after institutional review board approval, the medical records of patients with HAE at our institution who have received FFP since 1990 were reviewed to determine if there was evidence that FFP exacerbated the symptoms of HAE.

RESULTS: The English-language literature review and our patient medical record review failed to identify instances when FFP exacerbated symptoms of HAE or precipitated an attack. Several reports and our experience suggest that FFP is an effective prophylactic agent before surgery and for treatment of acute HAE attacks without evidence of exacerbation or initiation of symptoms.

CONCLUSIONS: FFP seems to be safe and effective in preventing exacerbations of HAE before surgery and for acute exacerbations of HAE without evidence of it initiating an attack or worsening a preexisting attack. [References: 26].

Apr;98(4):383-388

Available online at: annallergy.org/article/S1081-1206%2810%2960886-1/fulltext (small fee)

Visy B, Fust G, Bygum A, Bork K, Longhurst H, Bucher C, et al 6/2007 Helicobacter

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 patients with hereditary angioedema (HAE). The present study aimed to reinvestigate the relationship between H. pylori infection and the attack rate in the framework of an international collaborative study.

MATERIALS AND METHODS: Within the framework of the PREHAEAT project launched by the European Union, further 152 patients were studied in seven collaborating centers, and participants of the earlier study were followed up in order to detect any relationship between H. pylori infection and the occurrence of attacks in patients suffered from HAE.

RESULTS: The proportion of patients experiencing frequent (> 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 well. Nine subjects of the previous Hungarian study who underwent eradication therapy for dyspepsia were followed up for an additional 4 years. In these patients, attack frequency remained consistently low.

CONCLUSIONS: As shown by experience from the Hungarian and the international trial, the number 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 disease severity.

Jun;12(3):251-257

Available online at: onlinelibrary.wiley.com/doi/10.1111/j.1523-5378.2007.00501.x/full (small fee)

Bowen T, Cicardi M, Bork K, Zuraw B, Frank M, Ritchie B, et al /2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema

BACKGROUND: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) in 2004.

OBJECTIVE: To ensure that this consensus remains current.

METHODS: In collaboration with the Canadian Network of Rare Blood Disorder Organizations, we held the second Canadian Consensus discussion with our international colleagues in Toronto, Ontario, on February 3, 2006, and reviewed its content at the Fifth C1 Inhibitor Deficiency Workshop in Budapest on June 2, 2007. Papers were presented by international investigators, and this consensus algorithm approach resulted.

RESULTS: This consensus algorithm outlines the approach recommended for the diagnosis, therapy, and management of HAE, which was agreed on by the authors of this report. This document is only a consensus algorithm approach and continues to require validation. As such, participants agreed to make this a living 2007 algorithm, a work in progress, and to review its content at future international HAE meetings.

CONCLUSIONS: There is a paucity of double-blind, placebo-controlled trials on the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Controlled trials currently under way will provide further insight into the management of HAE. As with our Canadian 2003 Consensus, this 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of HAE was formed through the meeting and agreement of patient care professionals along with patient group representatives and individual patients. [References: 68].

Annals of Allergy, Asthma, & Immunology

Available online at: annallergy.org/article/S1081-1206%2810%2960584-4/fulltext (small fee)

Marco Cicardi, Konrad Bork, Bruce Zuraw, Mike Frank, Bruce Ritchie, Henriette Farkas, Lilian Varga, Lorenza C. Zingale, Karen Binkley, Eric Wagner, Peggy Adomaitis, Kristylea Brosz, Jeanne Burnham, Richard Warrington, Chrystyna Kalicinsky, Sean Mace, Christine McCusker, Robert Schellenberg, Lucia Celeste, Jacques Hebert, Karen Valentine, Man-Chiu Poon, Bazir Serushago, Doris Neurath, William Yang, Gina Lacuesta, Andrew Issekutz, Azza Hamed, Palinder Kamra, John Dean, Amin Kanani, Donald Stark, Georges-Etienne Rivard, Eric Leith, Ellie Tsai, Susan Waserman, Paul K. Keith, David Page, Silvia Marchesin, Hilary J. Longhurst, Wolfhart Kreuz, Eva Rusicke 12/2007 Annals of Allergy, Asthma & Immunology

BACKGROUND: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) in 2004.

OBJECTIVE: To ensure that this consensus remains current.

METHODS: In collaboration with the Canadian Network of Rare Blood Disorder Organizations, we held the second Canadian Consensus discussion with our international colleagues in Toronto, Ontario, on February 3, 2006, and reviewed its content at the Fifth C1 Inhibitor Deficiency Workshop in Budapest on June 2, 2007. Papers were presented by international investigators, and this consensus algorithm approach resulted.

RESULTS: This consensus algorithm outlines the approach recommended for the diagnosis, therapy, and management of HAE, which was agreed on by the authors of this report. This document is only a consensus algorithm approach and continues to require validation. As such, participants agreed to make this a living 2007 algorithm, a work in progress, and to review its content at future international HAE meetings.

CONCLUSIONS: There is a paucity of double-blind, placebo-controlled trials on the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Controlled trials currently under way will provide further insight into the management of HAE. As with our Canadian 2003 Consensus, this 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of HAE was formed through the meeting and agreement of patient care professionals along with patient group representatives and individual patients.

Available online at: dx.doi.org/10.1016/S1081-1206(10)60584-4

Farkas H, Jakab L, Temesszentandrasi G, Visy B, Harmat G, Fust G, et al 20/2007 Journal of Allergy & Clinical Immunology

BACKGROUND: C1-inhibitor (C1-INH) is a serine protease inhibitor regulating the complement, kinin-kallikrein, coagulation, and fibrinolytic systems. Hereditary angioedema (HAE) is caused by an inherited deficiency of C1-INH characterized by sudden, recurrent edematous swellings of the subcutaneous or submucosal tissues. The optional therapy for the acute management of HAE is administration of human C1-INH (hC1-INH) concentrate. However, hC1-INH is not available in many countries, in which case fresh frozen plasma is an alternative.

OBJECTIVE: To summarize our experience with hC1-INH concentrate in patients with HAE.

METHODS: Clinical and laboratory information on the effectiveness and safety of hC1-INH administered to relieve 468 acute edematous attacks in 61 patients with HAE was analyzed.

RESULTS: Severe abdominal or subcutaneous attacks and laryngeal edema were consistently relieved by the administration of 500 U hC1-INH concentrate. Symptoms improved within 15 to 60 minutes of administration. Progression of the attacks was never observed, and there were no recurrent attacks within 72 hours. hC1-INH concentrate requirements did not change after repeated use. hC1-INH concentrate proved effective in the management of 94 attacks in 22 children and 6 attacks in 4 pregnant women. Adverse reactions, viral infections, and antibody formation against the purified protein did not occur.

CONCLUSION: The administration of hC1-INH concentrate in HAE is highly effective and safe for the treatment of acute attacks and short-term prophylaxis and in pediatric patients and pregnant women.

CLINICAL IMPLICATIONS: Human C1-INH concentrate is effective and safe for the treatment of acute HAE attacks as well as for short-term prophylaxis.

Oct;120(4):941-947

Available online at: jacionline.org/article/S0091-6749%2807%2901246-8/fulltext

Sloane DE, Lee CW, Sheffer AL 9/2007 Journal of Allergy & Clinical Immunology

BACKGROUND: Attenuated androgens control attacks of hereditary angioedema. Short-term studies of such patients treated at our institution with attenuated androgens demonstrated no adverse effects. However, the side-effect frequencies in patients receiving long-term treatment are relatively less well characterized.

OBJECTIVE: To assess the frequencies of various side effects of the attenuated androgen stanozolol in a population of patients with hereditary angioedema treated for 20 to 40 years.

METHODS: Data on side effects in patients who continued stanozolol therapy since 1987 were obtained by means of questionnaire. Patients were evaluated by physical examination; biochemical assays of hepatic function, serum lipids, and prostate specific antigen; and liver ultrasound.

RESULTS: The minimal initial effective dosage of stanozolol was 0.5 to 2.0 mg daily, although most patients achieved symptomatic control and decreased the dose and frequency as the frequency of attacks decreased. Treatment-related symptoms developed in 10 of 21 patients. No interruption in stanozolol therapy was required because symptoms subsided with a reduction in the stanozolol dosage. Adverse side effects included hirsutism, weight gain, menstrual irregularities or postmenopausal bleeding, acne, and mood changes. Liver enzyme assays revealed no persistent abnormalities. Liver ultrasounds in 8 patients revealed 3 abnormalities deemed unrelated to therapy. Five patients had a reduced high-density lipoprotein, and 2 patients had elevated triglycerides.

CONCLUSION: Stanozolol is a safe and effective drug for the long-term management of hereditary angioedema.

CLINICAL IMPLICATIONS: Stanozolol may be used in the long-term treatment of patients with hereditary angioedema provided such patients are closely supervised with routine clinical, biochemical, and radiologic assessments.

Sep;120(3):654-658

Available online at: jacionline.org/article/S0091-6749%2807%2901265-1/fulltext

Gompels MM, Lock RJ 1/2007 Ann.Clin.Biochem.

BACKGROUND: C1 inhibitor deficiency may be hereditary or acquired. It is characterized by absent or poorly functioning C1 inhibitor. The disorder is rare, with prevalence estimated at 1/50,000. The very low incidence of the condition makes the sensitivity and specificity of assays used particularly important. Two different methods are commercially available to measure C1 inhibitor function. There are few data comparing these assays. METHODS: Two assays of C1 inhibitor function (C1 inhibitor-C1s complex formation or inhibition of C1 esterase cleavage of artificial substrate [colorimetric]) were compared in 71 patients (28 hereditary angioedema, 2 acquired angioedema and 41 controls). RESULTS: Qualitatively, the two assays showed good correspondence (92%). Six of 71 results were discordant. Correlation in quantitative terms was moderate (R = 0.81). CONCLUSIONS: Both assays show high sensitivity for hereditary/acquired angioedema. The colorimetric assay is more prone to false-positive results. However, clinical interpretation is not adversely affected.

Jan;44(Pt 1):75-78

Available online at: acb.sagepub.com/content/44/1/75.long (small fee)

Thon V, Harle P, Scholmerich J, Kuklinek P, Lokaj J, Straub RH 11/2007 Allergy

BACKGROUND: Hereditary angioedema (HAE) is successfully treated with danazol, a therapeutic steroid compound. To investigate hormones of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axis in patients with HAE with and without danazol.

METHODS: We included 16 patients with type I HAE, nine patients with type II HAE, and 16 healthy subjects. Serum levels of adrenocorticotropic hormone (ACTH), cortisol, androstenedione, dehydroepiandrosterone (DHEA), free testosterone, and 17beta-oestradiol were measured.

RESULTS: Serum levels of ACTH were markedly decreased in patients with type II HAE compared to the other groups (P < 0.001). Serum cortisol was similar between groups but danazol treatment decreased cortisol levels, particularly in women (P = 0.019). Serum levels of DHEA were significantly decreased in all patients with type I and II HAE compared to controls (P < 0.05), which was only partly dependent on prior danazol therapy as patients without danazol had also decreased serum levels of DHEA (P < 0.05). Furthermore, free testosterone serum levels were markedly increased in patients under danazol (P < 0.005) and the ratio of 17beta-oestradiol/free testosterone was significantly decreased in these patients (P < 0.005).

CONCLUSIONS: This study demonstrated decreased DHEA in patients with type I and II HAE independent of danazol therapy, which was particularly evident in women. It also demonstrates that danazol induced a marked up-regulation of free testosterone in relation to precursors and downstream 17beta-oestradiol. In HAE, there seems to be a primary lack of the adrenal androgen DHEA.

Nov;62(11):1320-1325

Available online at: onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.2007.01477.x/full

Farkas H, Varga L, Szeplaki G, Visy B, Harmat G, Bowen T 9/2007 Pediatrics

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. [References: 81].

Sep;120(3):e713-22

Available online at: pediatrics.aappublications.org/content/120/3/e713.full (small fee)

Choi G, Soeters MR, Farkas H, Varga L, Obtulowicz K, Bilo B, et al 6/2007 Transfusion

BACKGROUND: Patients with hereditary C1-inhibitor deficiency have recurrent attacks of angioedema, preferably treated with C1-inhibitor concentrate. A recombinant human C1-inhibitor (rHuC1INH) was developed, derived from milk from transgenic rabbits. This study was undertaken to investigate the effects of rHuC1INH in the treatment of acute angioedema attacks in patients with a hereditary C1-inhibitor deficiency.

STUDY DESIGN AND METHODS: Patients with hereditary C1-inhibitor deficiency were treated with rHuC1INH (at a dose of 100 U/kg) within 8 hours after onset of an acute attack. Time to initiation of relief and time to minimal symptoms were reported by both the patient and the treating physician.

RESULTS: Thirteen severe angioedema attacks in 9 patients with hereditary C1-inhibitor deficiency were treated with rHuC1INH. There was rapid improvement of clinical conditions for all attacks, with approximately 80 percent of treated patients experiencing symptom relief within 2 hours and minimal symptoms within 12 hours. There were no drug-related adverse events or immunogenic reactions to C1-inhibitor or rabbit proteins.

CONCLUSION: The transgenically produced rHuC1INH was successfully used in the treatment of acute angioedema attacks in patients with hereditary C1-inhibitor deficiency.

Jun;47(6):1028-1032

Available online at: onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2007.01239.x/full (small fee)

Cicardi M, Zingale LC /2007 Immunobiology

In this article, we review the traditional therapies of hereditary angioedema (HAE) that have been used for several years. Some of these therapies were proposed before the definition of the underlying defect and the understanding of the pathogenesis of the disease. We also describe new compounds under investigation at present as potential therapies for HAE. Two of these new therapies (a plasma-kallikrein inhibitor and a bradykinin B(2)-receptor antagonist) have been developed based on the understanding that the pathogenesis of symptoms was mainly due to kallikrein activation and bradykinin release. [References: 72].

212(4-5):325-331

Available online at: sciencedirect.com/science/article/pii/S0171298507000496 (small fee)

Cicardi M, Zingale LC, Zanichelli A, Deliliers DL, Caccia S 12/2007 Expert Opinion on Pharmacotherapy (Expert Opin.Pharmacother.)

C1-inhibitor (C1-INH) deficiency is the genetic defect underlying hereditary angioedema (HAE). Subjects with HAE suffer from recurrent angioedema that may result in death when it affects the larynx, severe abdominal pain when it affects the gastrointestinal mucosa and disfiguration when it affects the skin. The use of plasma-derived C1-INH concentrates to revert angioedema in HAE patients started in the 1970s. Since that time, three different preparations arrived onto the market, two of them are still present. Controlled studies and a large clinical experience indicate that C1-INH concentrate should be considered the treatment of choice for disabling angioedema attacks at any site. Efficacy has also been shown in preventing angioedema induced by invasive medical manoeuvres. Limited experience with repeated weekly infusions indicates that C1-INH can be used for long-term prophylaxis in selected patients. The safety profile is excellent and there are no reports of transmission of viral infections with the preparations available at present. C1-INH is licensed only in a limited number of countries. Clinical trials are ongoing at present to expand registration. [References: 84].

Dec;8(18):3173-3181

Available online at: tandfonline.com/doi/full/10.1517/14656566.8.18.3173 (small fee)

Bork K, Frank J, Grundt B, Schlattmann P, Nussberger J, Kreuz W 6/2007 Journal of Allergy & Clinical Immunology

BACKGROUND: In hereditary angioedema, bradykinin is assumed to be the most important mediator of edema formation.

OBJECTIVE: To assess whether the selective bradykinin receptor-2 antagonist Icatibant is effective in acute edema attacks of hereditary angioedema.

METHODS: In this uncontrolled pilot study, 15 patients with 20 attacks were treated with Icatibant. The attacks were analyzed by using a standardized and validated visual analog scale measurement and compared with historical data of untreated attacks. Plasma bradykinin concentration was measured before and 4 hours after intravenous Icatibant treatment.

RESULTS: Symptom intensity decreased within 4 hours after administration of Icatibant; the median time to onset of symptom relief was 1.50, 1.42, and 1.13 hours in the intravenous groups and 0.58 and 0.45 hours in the subcutaneous groups, respectively. The median difference in the 10-cm visual analog scale 4 hours after start of treatment was 4.11 cm (95% CI, 1.72-6.07). Compared with untreated attacks, Icatibant treatment reduced the mean (SD) time to onset of symptom relief by 97% from 42 +/- 14 to 1.16 +/- 0.95 hours (all groups combined). Median bradykinin concentration was 7-fold above the norm during acute attacks at 48.5 pmol/L and decreased to 18.0 pmol/L 4 hours after Icatibant infusion or injection.

CONCLUSION: Icatibant was effective in treating acute attacks of hereditary angioedema.

CLINICAL IMPLICATIONS: This is the first report demonstrating the clinical usefulness of antagonizing bradykinin binding to bradykinin receptor-2 in hereditary angioedema.

Jun;119(6):1497-1503

Available online at: jacionline.org/article/S0091-6749%2807%2900379-X/fulltext

Ott HW, Mattle V, Hadziomerovic D, Licht P, Doinghaus K, Rubbert A, et al 2/2007 Clin.Endocrinol.(Oxf)

OBJECTIVE: Eight women, aged 25-58 years, with hereditary angioneurotic oedema (HANE) were treated with tibolone, a synthetic steroid exhibiting oestrogenic, androgenic and progestational activity.

DESIGN: Pilot study.

RESULTS: Tibolone at a dose of 2.5-7.5 mg/day significantly reduced the number and severity of attacks and the number of ampoules of C1-esterase inhibitor (C1-INH) needed for symptomatic therapy. The efficacy of tibolone was comparable to that of danazol, while the androgenic side-effects were considerably reduced.

CONCLUSIONS: Tibolone may represent an alternative to danazol administration for the prophylaxis of HANE in women.

Feb;66(2):180-184

Available online at: onlinelibrary.wiley.com/wol1/doi/10.1111/j.1365-2265.2006.02704.x/full (small fee)