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WMJ : Official Publication of the State... Apr 2022Hereditary angioedema (HAE) is a rare and disabling disorder wherein there is excessive bradykinin production, with subsequent increased vascular permeability in the... (Review)
Review
Hereditary angioedema (HAE) is a rare and disabling disorder wherein there is excessive bradykinin production, with subsequent increased vascular permeability in the superficial tissues and gastrointestinal and respiratory mucosa. This article serves as a review of the pathogenesis of the disease, as well as an update of the evidence-based new treatment recommendations to help clinicians with the diagnosis and management of HAE.
Topics: Angioedemas, Hereditary; Blindness; Bradykinin; Complement C1 Inhibitor Protein; Humans
PubMed: 35442579
DOI: No ID Found -
Journal of Investigational Allergology... Feb 2021Hereditary angioedema due to C1-esterase inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease. In the last decade, new drugs and new indications for... (Review)
Review
Hereditary angioedema due to C1-esterase inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease. In the last decade, new drugs and new indications for old drugs have played a role in the management of C1-INH-HAE. This review examines current therapy for C1-INH-HAE and provides a brief summary of drugs that are under development. Increased knowledge of the pathophysiology of C1-INH-HAE has been crucial for advances in the field, with inhibition of the kallikrein-kinin system (plasma kallikrein, activated factor XII) as a key area in the discovery of new drugs, some of which are already marketed for treatment of C1-INH-HAE. Pharmacological treatment is based on 3 pillars: treatment of acute angioedema attacks (on-demand treatment), short-term (preprocedure) prophylaxis, and long-term prophylaxis. The 4 drugs that are currently available for the treatment of acute angioedema attacks (purified plasma-derived human C1 esterase inhibitor concentrate, icatibant acetate, ecallantide, recombinant human C1 esterase inhibitor) are all authorized for self-administration, except ecallantide. Purified plasma-derived human C1 esterase inhibitor concentrate is the treatment of choice for short-term prophylaxis. Tranexamic acid, danazol, intravenous and subcutaneous nanofiltered purified plasma-derived human C1 esterase inhibitor concentrate, and lanadelumab can be used for long-term prophylaxis. New drugs are being investigated, mainly as long-term prophylaxis, and are aimed at blocking the kallikrein-kinin system by means of antiprekallikrein, antikallikrein, and anti-activated FXII action.
Topics: Angioedemas, Hereditary; Anti-Inflammatory Agents, Non-Steroidal; Bradykinin; Complement C1 Inhibitor Protein; Humans; Kallikrein-Kinin System; Peptides; Recombinant Proteins
PubMed: 33602658
DOI: 10.18176/jiaci.0653 -
Function (Oxford, England) 2021
Topics: Humans; Bradykinin; COVID-19; Pancreatitis; Pancreas
PubMed: 34642664
DOI: 10.1093/function/zqab046 -
International Journal of Molecular... Aug 2021Angioedema is a life-threatening emergency event that is associated with bradykinin and histamine-mediated cascades. Although bradykinin-mediated angioedema currently... (Review)
Review
Angioedema is a life-threatening emergency event that is associated with bradykinin and histamine-mediated cascades. Although bradykinin-mediated angioedema currently has specific therapeutic options, angioedema is sometimes intractable with current treatments, especially histamine-mediated angioedema, suggesting that some other mediators might contribute to the development of angioedema. Fatty acids are an essential fuel and cell component, and act as a mediator in physiological and pathological human diseases. Recent updates of studies revealed that these fatty acids are involved in vascular permeability and vasodilation, in addition to bradykinin and histamine-mediated reactions. This review summarizes each fatty acid's function and the specific receptor signaling responses in blood vessels, and focuses on the possible pathogenetic role of fatty acids in angioedema.
Topics: Angioedema; Bradykinin; Capillary Permeability; Fatty Acids; Histamine; Humans; Prostaglandins
PubMed: 34445711
DOI: 10.3390/ijms22169000 -
Deutsches Arzteblatt International Jul 2017Acute angioedema of the upper airways can be life-threatening. An important distinction is drawn between mast-cell-mediated angioedema and bradykinin-mediated... (Review)
Review
BACKGROUND
Acute angioedema of the upper airways can be life-threatening. An important distinction is drawn between mast-cell-mediated angioedema and bradykinin-mediated angioedema; the treatment of these two entities is fundamentally different.
METHODS
This review is based on pertinent articles retrieved by a selective search in PubMed and on guidelines concerning the treatment of angioedema. The authors draw on their own clinical experience in their assessment of the literature.
RESULTS
In the emergency clinical situation, the most important information comes from accompanying manifestations such as itching and urticaria and from the patient's drug history and family history. When angioedema affects the head and neck, securing the upper airways is the highest priority. Angioedema is most commonly caused by mast-cell mediators, such as histamine. This type of angioedema is sometimes accompanied by urticaria and can be effectively treated with antihistamines or glucocorticoids. In case of a severe allergic reaction or anaphylaxis, epinephrine is given intramuscularly in a dose that is adapted to the patient's weight (150 μg for body weight >10 kg, 300 μg for body weight >30 kg). Bradykinin-mediated angioedema may arise as either a hereditary or an acquired tendency. Acquired angioedema can be caused by angiotensin converting enzyme (ACE) inhibitors and by angiotensin II receptor blockers. Bradykinin-mediated angioedema should be treated specifically with C1-esterase inhibitor concentrates or bradykinin-2 receptor antagonists.
CONCLUSION
Angioedema of the upper airways requires a well-coordinated diagnostic and therapeutic approach. Steroids and antihistamines are very effective against mast-cell-mediated angioedema, but nearly useless against bradykinin-mediated angioedema. For angioedema induced by ACE inhibitors, no causally directed treatment has yet been approved.
Topics: Anaphylaxis; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Drug Hypersensitivity; Glucocorticoids; Histamine Antagonists; Humans
PubMed: 28818177
DOI: 10.3238/arztebl.2017.0489 -
Polskie Archiwum Medycyny Wewnetrznej 2016Angioedema and urticaria often constitute a challenge in daily clinical practice. They may either co- -occur or present as independent conditions. They are characterized... (Review)
Review
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.
Topics: Angioedema; Angioedemas, Hereditary; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Humans
PubMed: 26842379
DOI: 10.20452/pamw.3273 -
Molecular Medicine (Cambridge, Mass.) Nov 2020The response to viral infection generally includes an activation of the adaptive immune response to produce cytotoxic T cells and neutralizing antibodies. We propose... (Review)
Review
The response to viral infection generally includes an activation of the adaptive immune response to produce cytotoxic T cells and neutralizing antibodies. We propose that SARS-CoV-2 activates the innate immune system through the renin-angiotensin and kallikrein-bradykinin pathways, blocks interferon production and reduces an effective adaptive immune response. This model has therapeutic implications.
Topics: Animals; Betacoronavirus; Bradykinin; COVID-19; Coronavirus Infections; Humans; Immunity, Innate; Kallikreins; Models, Immunological; Pandemics; Pneumonia, Viral; Renin-Angiotensin System; SARS-CoV-2
PubMed: 33167852
DOI: 10.1186/s10020-020-00231-w -
International Journal of Molecular... Jul 2023Bradykinin (BK) metabolism and its receptors play a central role in drug-induced angioedema (AE) without urticaria through increased vascular permeability. Many... (Review)
Review
Bradykinin (BK) metabolism and its receptors play a central role in drug-induced angioedema (AE) without urticaria through increased vascular permeability. Many cardiovascular and diabetic drugs may cause BK-mediated AE. Angiotensin-converting enzyme inhibitors (ACEIs) and neprilysin inhibitors impair BK catabolism. Dipeptidyl peptidase-IV (DPP-IV) inhibitors reduce the breakdown of BK and substance P (SP). Moreover, angiotensin receptor blockers, thrombolytic agents, and statins may also induce BK-mediated AE. Understanding pathophysiological mechanisms is crucial for preventing and treating drug-induced AE.
Topics: Humans; Angioedema; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Dipeptidyl-Peptidase IV Inhibitors; Fibrinolytic Agents
PubMed: 37511409
DOI: 10.3390/ijms241411649 -
The Journal of Allergy and Clinical... 2017
Topics: Angioedema; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Humans
PubMed: 29122164
DOI: 10.1016/j.jaip.2017.07.040 -
Frontiers in Immunology 2021Angioedema is a prevailing symptom in different diseases, frequently occurring in the presence of urticaria. Recurrent angioedema without urticaria (AE) can be... (Review)
Review
Angioedema is a prevailing symptom in different diseases, frequently occurring in the presence of urticaria. Recurrent angioedema without urticaria (AE) can be hereditary (HAE) and acquired (AAE), and several subtypes can be distinguished, although clinical presentation is quite similar in some of them. They present with subcutaneous and mucosal swellings, affecting extremities, face, genitals, bowels, and upper airways. AE is commonly misdiagnosed due to restricted access and availability of appropriate laboratorial tests. HAE with C1 inhibitor defect is associated with quantitative and/or functional deficiency. Although bradykinin-mediated disease results mainly from disturbance in the kallikrein-kinin system, traditionally complement evaluation has been used for diagnosis. Diagnosis is established by nephelometry, turbidimetry, or radial immunodiffusion for quantitative measurement of C1 inhibitor, and chromogenic assay or ELISA has been used for functional C1-INH analysis. Wrong handling of the samples can lead to misdiagnosis and, consequently, mistaken inappropriate approaches. Dried blood spot (DBS) tests have been used for decades in newborn screening for certain metabolic diseases, and there has been growing interest in their use for other congenital conditions. Recently, DBS is now proposed as an efficient tool to diagnose HAE with C1 inhibitor deficiency, and its use would improve the access to outbound areas and family members. Regarding HAE with normal C1 inhibitor, complement assays' results are normal and the genetic sequencing of target genes, such as exon 9 of and , is the only available method. New methods to measure cleaved high-molecular-weight kininogen and activated plasma kallikrein have emerged as potential biochemical tests to identify bradykinin-mediated angioedema. Validated biomarkers of kallikrein-kinin system activation could be helpful in differentiating mechanisms of angioedema. Our aim is to focus on the capability to differentiate histaminergic AE from bradykinin-mediated AE. In addition, we will describe the challenges developing specific tests like direct bradykinin measurements. The need for quality tests to improve the diagnosis is well represented by the variability of results in functional assays.
Topics: Angioedema; Angioedemas, Hereditary; Biomarkers; Bradykinin; Complement C1 Inhibitor Protein; DNA Mutational Analysis; Diagnosis, Differential; Diagnostic Errors; Dried Blood Spot Testing; Enzyme-Linked Immunosorbent Assay; Factor XII; Humans; Mutation; Plasminogen; Recurrence
PubMed: 34956216
DOI: 10.3389/fimmu.2021.785736