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Ann Allergy Asthma Immunol 2019 Apr 17. Epub 2019 Apr 17.

Allergy 2019 Apr 20. Epub 2019 Apr 20.

Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Strasse 10, 13125, Berlin, Germany.

Pediatr Allergy Immunol 2019 Apr 16. Epub 2019 Apr 16.

Charité Universitätsmedizin Berlin, Berlin, Germany.

Background: Attacks of hereditary angioedema (HAE) due to C1 esterase inhibitor deficiency (C1-INH-HAE) usually begin during childhood or adolescence. However, limited data are available regarding indications and modalities of treatment of children. This study evaluated recombinant human C1-INH (rhC1-INH) for HAE attacks in children. Read More

Pediatr Allergy Immunol 2019 Apr 9. Epub 2019 Apr 9.

HRZM Hemophilie Center Rhein Main, Mörfelden-Walldorf, Germany.

Background: Patients with hereditary angioedema with C1 inhibitor deficiency or dysfunction have burdensome recurrent angioedema attacks. The safety, efficacy, and health-related quality of life (HRQoL) outcomes of C1 inhibitor (C1-INH) prophylaxis (intravenously administered) in patients aged 6-11 years were investigated.

Methods: Eligible patients were enrolled in a randomized, single-blind, crossover phase 3 trial. Read More

J Biol Chem 2019 Apr 5. Epub 2019 Apr 5.

Department of Biochemistry, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/C, Hungary.

The lectin pathway (LP) of the complement system is an important anti-microbial defense mechanism, but it also contributes significantly to ischemia reperfusion injury (IRI) associated with myocardial infarct, stroke and several other clinical conditions. Mannan-binding lectin (MBL)-associated serine proteinase 2 (MASP-2) is essential for LP activation and therefore it is a potential drug target. We have previously developed the first two generations of MASP-2 inhibitors by in vitro evolution of two unrelated canonical serine proteinase inhibitors. Read More

Int J Psychiatry Med 2019 Mar 29:91217419837068. Epub 2019 Mar 29.

1 Department of Psychiatry, Ege University Faculty of Medicine, Izmir, Turkey.

Objective: Hereditary angioedema is a serious disease with unpredictable attacks. It has an impact on patients' health-related quality of life. This study aimed to assess the quality of life of the hereditary angioedema patients and to investigate the relationship between quality of life and demographic, clinical, laboratory, and psychiatric parameters. Read More

Case Rep Genet 2019 24;2019:7052062. Epub 2019 Feb 24.

Division of Clinical Immunology, Department of Pathology, Queen Mary Hospital, Hong Kong.

We report a heterozygous, 2,009 base pairs (bps) genomic DNA deletion within the gene that has not previously been reported in a case of type I hereditary angioedema (HAE). The patient is a 28-year-old Han Chinese female living in Hong Kong who has suffered from recurrent angioedema since adolescence, with increasing attack frequency as she entered adulthood; in the past, episodes occurred annually, but now occur every two to three months. The affected areas are not itchy and include common sites such as the left and right forearms, but without throat involvement. Read More

Transfus Apher Sci 2019 Mar 14. Epub 2019 Mar 14.

Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan; International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan. Electronic address:

Since the first successful transfusion in 1818, Transfusion Medicine has evolved significantly. The advent of plasma fractionation and availability of recombinant products allowed for precision replacement therapy to treat many hematological conditions, such as hemophilia, thrombotic thrombocytopenic purpura, and hereditary angioedema. A deeper understanding of the pathophysiology underlying those conditions along with the development of safer monoclonal and bispecific antibodies is now offering safe and effective alternatives to the simple conventional approach of replacing a missing plasma protein. Read More

Intern Med 2019 Mar 28. Epub 2019 Mar 28.

Department of Neurology, Nagoya University Graduate School of Medicine, Japan.

A 41-year-old woman presented with recurrent dizziness. After an attack of dizziness, she felt edematous sensations in her hands. However, according to photographs taken during the attack, the edema on the back of the patient' s hands and fingers appeared mild. Read More

Br J Anaesth 2019 Mar 12. Epub 2019 Mar 12.

Department of Anaesthesia and Peri-operative Medicine, Auckland City Hospital, Auckland, New Zealand.

This narrative review seeks to distinguish the clinical patterns of pre-existing allergic conditions from other confounding non-allergic clinical entities, and to identify the potential related risks and facilitate their perioperative management. Follow-up investigation should be performed after a perioperative immediate hypersensitivity to establish a diagnosis and provide advice for subsequent anaesthetics, the main risk factor for perioperative immunoglobulin E (IgE)-mediated anaphylaxis being a previous uninvestigated perioperative immediate hypersensitivity reaction. The concept of cross-reactivity between drugs used in the perioperative setting and food is often quoted, but usually not supported by evidence. Read More

Expert Opin Biol Ther 2019 Mar 26:1-10. Epub 2019 Mar 26.

b Department of Biomedical and Clinical Sciences Luigi Sacco , University of Milan , Milan , Italy.

Introduction: Hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) is a rare disease with unpredictable, self-limiting and localized swelling episodes involving the cutaneous and subcutaneous tissues. In the last decade, the spectrum of the possibilities to control the disease has considerably changed with the development of biologic therapies making necessary a careful evaluation of the differences among current and emerging treatments to properly optimize the management of patients. Areas covered: This review serves to summarize the literature regarding the use of biologics for the treatment of C1-INH-HAE. Read More

Vnitr Lek 2019 ;65(2):109-116

In contrast to general opinion, the issue of primary immunodeficiency is far from just a pediatric medicine; a large number of patients with primary immunodefciencies are not only treated, but also diagnosed in adulthood. The most important manifestation of these diseases are serious, unusual or ill-treatable infections. Some primary immune deficiency diseases manifest themselves in adulthood - mainly common variable immunodeficiency (CVID) and Goods syndrome (hypogammaglobulinemia with thymoma). Read More

Allergy 2019 Mar 25. Epub 2019 Mar 25.

HAE Centre Denmark, Odense University Hospital, Odense, Denmark.

Allergy Asthma Clin Immunol 2019 7;15:13. Epub 2019 Mar 7.

AMF Consulting, Inc., Los Angeles, CA USA.

Introduction: For prophylaxis of hereditary angioedema (HAE) attacks, replacement therapy with human C1-inhibitor (C1-INH) treatment is approved and available as intravenous [C1-INH(IV)] (Cinryze) and subcutaneous [C1-INH(SC)] HAEGARDA preparations. In the absence of a head-to-head comparative study of the two treatment modalities, an indirect comparison of data from 2 independent but similar clinical trials was undertaken.

Methods: Two similar randomized, double-blind, placebo-controlled, crossover studies were identified which evaluated either C1-INH(SC) (COMPACT; NCT01912456; 16 weeks) or C1-INH(IV) (CHANGE; NCT01005888; 14 weeks) vs. Read More

Orphanet J Rare Dis 2019 Mar 18;14(1):67. Epub 2019 Mar 18.

Department of Family Medicine, Semmelweis University, Budapest POB 2, Kútvölgyi str. 4, Budapest, H-1125, Hungary.

Background And Aims: Hereditary angioedema with C1-inhibitor deficiency (C1-INH-HAE) is characterized by localized, non-pitting, and transient swelling of submucosal or subcutaneous region. Human fetuin-A is a multifunctional glycoprotein that belongs to the proteinase inhibitor cystatin superfamily and has structural similarities to the high molecular weight kininogen. Fetuin-A is also known a negative acute phase reactant with anti-inflammatory characteristics. Read More

Anesth Prog 2019 ;66(1):30-32

Department of Dental Anesthesiology, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.

Hereditary angioedema (HAE) is a rare genetic disease that results from deficiency or dysfunction of C1 inhibitor (C1-INH). This disease is characterized by sudden attacks of angioedema. When edema occurs in the pharynx or larynx, it can lead to serious airway compromise, including death. Read More

J Dtsch Dermatol Ges 2019 Apr 18;17(4):416-423. Epub 2019 Mar 18.

Department of Dermatology and Venereology, Medical University of Graz, Austria.

Background: Data on the prevalence and clinical features of Austrian patients with hereditary angioedema (HAE) with C1-inhibitor (C1-INH) deficiency (HAE-1) or dysfunction (HAE-2) are lacking.

Methods: Current baseline data were collected in a national survey. The records of HAE patients at the Medical University of Graz were analyzed with regard to clinical characteristics. Read More

J Struct Biol 2019 Mar 12. Epub 2019 Mar 12.

Global Blood Therapeutics, South San Francisco, CA 94080, United States.

Plasma kallikrein (pKal) is a serine protease responsible for cleaving high-molecular-weight kininogen to produce the pro-inflammatory peptide, bradykinin. Unregulated pKal activity can lead to hereditary angioedema (HAE) following excess bradykinin release. HAE attacks can lead to a compromised airway that can be life threatening. Read More

Eur J Pharm Sci 2019 Apr 6;132:121-124. Epub 2019 Mar 6.

Institute of Chemistry - Analytical Chemistry for Health and Environment, University of Universitaetplatz 1, Graz, Austria.

Icatibant is a peptidomimetic drug serving as a bradykinin-receptor antagonist and is approved in Europe and the United States for the treatment of hereditary angioedema attacks. We have detected an impurity with a high structural similarity to icatibant in pharmaceutical dosage forms using an optimized chromatographic method based on reversed phase high performance liquid chromatography with UV detection. The abundance of the impurity was around 1% relative to the icatibant peak following storage at room temperature for 1 month, and raised up to ~16% upon temperature stressing at 100 °C. Read More

Front Med (Lausanne) 2019 21;6:28. Epub 2019 Feb 21.

Department of Biophysics, Federal University of São Paulo, São Paulo, Brazil.

Hereditary angioedema (HAE) is an autosomal dominant disease caused by C1-INH deficiency due to mutations in (C1-INH-HAE) in most of the cases, or by specific mutations in factor XII gene, (F12-HAE). Identification of polymorphisms in the genes encoding proteins from key pathways driving HAE can help to understand how genetic diversity contributes to its phenotypic variability. Here, 15 genes related to the Kallikrein-Kinin System (KKS) were analyzed by next generation sequencing in 59 patients with C1-INH-HAE or F12-HAE from Brazil, Denmark and Spain, and 19 healthy relatives in a total of 31 families. Read More

BMJ Case Rep 2019 Mar 4;12(3). Epub 2019 Mar 4.

Department of Dermatology and Allergy Center, University Hospital of Odense, Odense, Denmark.

Hereditary angioedema (HAE) is a relapsing swelling disorder which can cause severe pain, affect quality of life and potentially be life threatening with involvement of the airways. We present a 34-year-old immigrant who suffered from very frequent and severe HAE attacks. The attacks often involved the face, mouth and the airways. Read More

Open Access Maced J Med Sci 2019 Feb 13;7(3):369-372. Epub 2019 Feb 13.

Department of Microbiology and Immunology, Faculty of Pharmacy, Medical University-Plovdiv, Plovdiv, Bulgaria.

Background: Angioneurotic oedema (AE) is an unpredictable and dangerous disease directly threatening the patient's life due to a sudden onset of upper respiratory tract obstruction. The disease is associated with various causes and triggering factors, but little is known about the conditions that accompany AE.

Aim: The study aims to determine the age-specificities and the spectrum of concomitant diseases in patients with AE. Read More

Ann Allergy Asthma Immunol 2019 Mar 1. Epub 2019 Mar 1.

Immunology Department, St Helier Hospital, Surrey, United Kingdom.

Eur J Dermatol 2019 Feb;29(1):14-20

Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.

Hereditary angioedema (HAE) is a rare autosomal dominant disorder of vascular permeability associated with heterogeneous clinical manifestations, with prevalence estimated at 1/50,000. Most disease-causing variants lie within the SERPING1 gene, while FXII12, PLG and ANGPT1 gene variants are also reported to associate with HAE. Research on HAE in China began in the 1980s, and later studies identified some clinical characteristics of Chinese HAE patients that differ from the western population. Read More

J Allergy Clin Immunol Pract 2019 Feb 27. Epub 2019 Feb 27.

Department of Medicine, Allergy and Immunology Section, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia. Electronic address:

Allergy Asthma Proc 2019 Mar;40(2):103-110

University of Puerto Rico School of Medicine, San Juan, Puerto Rico.

There is limited data on clinical characteristics and quality of life (QoL) of Hereditary angioedema (HAE) patients in Puerto Rico. Create an epidemiological and clinical profile of patients with HAE and assess the burden of this condition on the general health of Puerto Ricans suffering the disease. A cross-sectional study was performed in 32 Puerto Rican patients with HAE. Read More

Nucleic Acid Ther 2019 Apr 28;29(2):82-91. Epub 2019 Feb 28.

Ionis Pharmaceuticals, Inc., Carlsbad, California.

Kallikrein is the key contact system mediator responsible for the conversion of high-molecular-weight kininogen into the inflammatory vasodilator peptide bradykinin, a process regulated by C1-esterase inhibitor (C1-INH). In hereditary angioedema (HAE), genetic mutations result in deficient or dysfunctional C1-INH and dysregulation of the contact system leading to recurrent, sometimes fatal, angioedema attacks. IONIS-PKK is a second-generation 2'-O-(2-methoxyethyl)-modified chimeric antisense oligonucleotide, designed to bind and selectively reduce prekallikrein (PKK) mRNA in the liver. Read More

Front Med (Lausanne) 2019 12;6:25. Epub 2019 Feb 12.

Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.

Excessive enzyme activity often has pathological consequences. This for example is the case in thrombosis and hereditary angioedema, where serine proteases of the coagulation system and kallikrein-kinin system are excessively active. Serine proteases are controlled by SERPINs (serine protease inhibitors). Read More

Clin Transl Allergy 2019 14;9. Epub 2019 Feb 14.

1Department of Dermatology, Allergology and Venereology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.

Hereditary angioedema (HAE) is a life-threatening disease characterized by recurrent episodes of subcutaneous and mucosal swellings and abdominal cramping. Corticosteroids and antihistamines, which are usually beneficial in histamine-induced acquired angioedema, are not effective in HAE. Therefore, diagnosing HAE correctly is crucial for affected patients. Read More

Arerugi 2019;68(1):16-19

Department of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima University.

J Allergy Clin Immunol Pract 2019 Feb 15. Epub 2019 Feb 15.

CSL Behring LLC, King of Prussia, Pa.

Background: For the prevention of attacks of hereditary angioedema (HAE), the efficacy and safety of subcutaneous human C1-esterase inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) was established in the 16-week Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1-Inhibitor Replacement Therapy (COMPACT).

Objective: To assess the long-term safety, occurrence of angioedema attacks, and use of rescue medication with C1-INH(SC).

Methods: Open-label, randomized, parallel-arm extension of COMPACT across 11 countries. Read More

J Allergy Clin Immunol Pract 2019 Feb 12. Epub 2019 Feb 12.

Division of Allergy and Clinical Immunology, Department of Medicine, East Tennessee State University, Johnson City, Tenn. Electronic address:

Pediatr Int 2019 Jan;61(1):101-103

Department of Pediatrics, Tokyo Women's Medical University Medical Center East, Tokyo, Japan.

J Allergy Clin Immunol Pract 2019 Feb;7(2):754

Allergy/Immunology Associates Inc, Mayfield Heights, Ohio.

Ann Allergy Asthma Immunol 2019 Feb;122(2):228-229

Department of Medical Sciences and Public Health, Unit of Internal Medicine, Allergy and Clinical Immunology, University of Cagliari, Italy.

J Nephrol 2019 Jan 30. Epub 2019 Jan 30.

Department of Emergency and Organ Transplantation, Nephrology, Dialysis and Transplantation Unit, University of Bari, Bari, Italy.

Urinary tract infections (UTIs) after kidney transplantation are associated with significant morbidity. However, data on the impact of UTI on graft survival are controversial. We conducted a retrospective cohort study of 380 kidney transplant patients. Read More

J Manag Care Spec Pharm 2019 Feb;25(2):148-151

1 Division of Rheumatology, Allergy and Immunology, Department of Medicine, University of California San Diego School of Medicine and Medicine Service, San Diego VA Healthcare.

Disclosures: No funding supported the writing of this commentary. The author reports personal fees from BioCryst, CSL Behring, Shire, and Pharming and grants from Ionis. He is chair of the US HAEA Medical Advisory Board and scientific advisor for HAE International. Read More

J Manag Care Spec Pharm 2019 Feb;25(2):143-148

1 Institute for Clinical and Economic Review, Boston, Massachusetts.

Disclosures: Funding for this summary was contributed by the Laura and John Arnold Foundation, Blue Shield of California, and California Health Care Foundation to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, AHIP Anthem, Blue Shield of California, CVS Caremark, Express Scripts, Harvard Pilgrim Health Care, Cambia Health Solutions, United Healthcare, Kaiser Permanente, Premera Blue Cross, AstraZeneca, Genentech, GlaxoSmithKline, Johnson & Johnson, Merck, National Pharmaceutical Council, Prime Therapeutics, Sanofi, Spark Therapeutics, Health Care Service Corporation, Editas, Alnylam, Regeneron, Mallinkrodt, Biogen, HealthPartners, and Novartis. Agboola, Dreitlein, and Pearson are ICER employees. Read More

Arch Med Sci 2019 01 31;15(1):92-98. Epub 2017 Jul 31.

School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Introduction: Hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) or with normal C1-INH is characterized by recurrent swellings due to uncontrolled production of vasoactive mediators, among which bradykinin (BK) is crucial. Through the binding and activation of the two human BK-receptors, kinins may have dual beneficial and deleterious effects in vascular and inflammation physiopathology by inducing oxidative stress. We aimed to assess the serum concentrations of advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs) in patients affected by HAE. Read More

Pediatr Allergy Immunol 2019 Jan 28. Epub 2019 Jan 28.

Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Clin Exp Allergy 2019 Jan 28. Epub 2019 Jan 28.

Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.

Background: Different mutations of the angiopoietin-1 gene (ANGPT1) have been associated with the occurrence of hereditary angioedema (HAE).

Objective: The purpose of the study is to clarify whether the ANGPT1 A119S variant plays its role via haploinsufficiency or a dominant negative effect.

Methods: The ability of ANGPT1 A119S variant to affect the endothelial barrier function was assessed by immunocytochemistry. Read More

Mol Immunol 2019 03 24;107:91-96. Epub 2019 Jan 24.

Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic; Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.

Mutations in the C1 inhibitor (C1INH) encoding gene, SERPING1, are associated with hereditary angioedema (HAE) which manifests as recurrent submucosal and subcutaneous edema episodes. The major C1INH function is the complement system inhibition, preventing its spontaneous activation. The presented study is focused on SERPING1 exon 3, an alternative and extraordinarily long exon (499 bp). Read More

J Allergy Clin Immunol Pract 2019 Jan 23. Epub 2019 Jan 23.

Hungarian Angioedema Reference Center, Semmelweis University, Budapest, Hungary.

Background: Hereditary angioedema (HAE) with C1 inhibitor deficiency (C1-INH) is characterized by swelling of subcutaneous and/or submucosal tissues.

Objective: To evaluate efficacy/safety of fixed-dose subcutaneous plasma-derived C1-INH (pdC1-INH) liquid for HAE attack prevention (NCT02584959).

Methods: Eligible patients were ≥12 years with ≥2 monthly attacks prescreening or pre-long-term prophylaxis. Read More

Exp Ther Med 2019 Feb 16;17(2):1068-1072. Epub 2018 Nov 16.

Allergology and Immunology Discipline, 'Iuliu Hațieganu' University of Medicine and Pharmacy, Cluj-Napoca 400012, Romania.

Angioedema can occur in isolation, accompanied by urticaria, or as a feature of anaphylaxis in mast cell-mediated disorders, bradykinin-mediated disorders, as well as in others with unknown mechanisms, such as infections, rare disorders, or idiopathic angioedema. In mast cell-mediated angioedema, other signs and symptoms of mast cell-mediator release are frequently seen. However, clear evidence of mast cell degranulation may be absent in histaminergic angioedema. Read More

J Allergy Clin Immunol Pract 2019 Jan 17. Epub 2019 Jan 17.

Department of Immunology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

Hautarzt 2019 Feb;70(2):107-115

Klinik für Dermatologie, Venerologie und Allergologie, Allergie-Centrum-Charité/ECARF, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Deutschland.

Angioedema is a spontaneous, edematous swelling of the deep layers of the skin or mucous membrane. Angioedema in the respiratory tract is potentially life-threatening. The classification of angioedema into mast-cell-mediated (e. Read More

Hautarzt 2019 Feb;70(2):101-106

Spezialsprechstunde Angioödeme, Hautklinik und Poliklinik, Universitätsmedizin Mainz, Langenbeckstr. 1, 55131, Mainz, Deutschland.

Manifestation of angioedema can occur at any age. We distinguish between two main subtypes: mast cell mediator-associated angioedema (often with hives) and the non-mast cell mediator-associated angioedema. The patient's history is very important due to the fact that one subtype can be hereditary, but we also have to consider new mutations and even not yet diagnosed patients. Read More

Res Pract Thromb Haemost 2019 Jan 16;3(1):38-43. Epub 2018 Dec 16.

Department of Molecular Cell Biology Sanquin Research & Landsteiner Laboratory Amsterdam The Netherlands.

Congenital deficiency of C1 inhibitor, the main inhibitor of the classic complement system pathway, leads to paroxysmal angioedema (hereditary angioedema) that can be debilitating or life-threatening for affected patients. In the past few years many new insights on the pathogenesis of angioedema formation in the presence of low levels of C1 inhibitor has been accumulated. There is a central role for bradykinin that is released upon activation of the kallikrein-kinin system that is insufficiently controlled by adequate levels of C1 inhibitor. Read More