Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042109 (urticaria)
 6,569 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies show that oral antihistamines affect the weal and flare response to intradermal injections of the inflammatory mediators platelet-activating factor (PAF) and bradykinin (BK). The aim of this study was to compare the effects of terfenadine (an H1-antagonist) and cimetidine (an H2-antagonist) on weal and flare responses to PAF and BK in healthy non-atopic human volunteers. The effects of doxepin on PAF responses were investigated, as there is evidence that doxepin may have direct anti-PAF effects in addition to its known antihistaminic actions. Terfenadine significantly reduced weal and flare responses to PAF (mean reduction 53 and 73%, respectively) and flare responses to BK (mean reduction 78%) but had no effect on weal responses to BK. Doxepin significantly reduced both weal and flare responses to PAF (mean reduction 43 and 68%, respectively, at higher doses of PAF). Cimetidine had no effect on weal or flare responses to PAF or BK. These findings suggest that the flare response to intradermal BK is mediated via histamine release while the weal response is not. The effects of the various antagonists of PAF-induced responses suggest that its effects too may be mediated via histamine, the similarity of the effects of terfenadine and doxepin on these responses indicating that the effects of doxepin may be due to its known antihistamine activity rather than to any specific PAF-antagonistic properties. Platelet-activating factor (PAF) is a phospholipid which is released from a wide range of cell types and also from vascular endothelium. PAF is formed by the conversion of ether-linked phospholipids initially to the biologically inactive lyso-PAF and then by acetylation to PAF. Intradermal injection of PAF in human skin causes vasodilatation and increased vascular permeability, producing a weal and flare response with accompanying pruritus. Bradykinin (BK) is a vasoactive polypeptide formed by the action of enzymes known as kallikreins on inactive precursors called kininogens. Its effects include an increase in blood flow and vascular permeability and stimulation of the release of prostaglandins and histamine. On intradermal injection in human skin it causes a weal and flare response with associated pain rather than pruritus. Previous studies have suggested that the weal and flare response to PAF may be mediated in part by histamine release. Given that BK is known to cause histamine release it appears possible that the responses to both compounds may be modified by conventional antihistamines. Experiments based on this premise have found that antihistamines have a pronounced effect on the flare response to PAF but a less marked effect on weal responses. The weal response to BK was unaffected by systemic antihistamines but studies have produced conflicting results with regard to effects on the flare response. The aim of this study was to compare the effects of terfenadine (an H1-antagonist) and cimetidine (an H2-antagonist) on PAF- and BK-induced weal and flare responses in healthy, non-atopic human volunteers. Based on the treatment of cold urticaria it has been suggested that doxepin, which has known H1- and H2-antagonistic effects, may in addition show specific anti-PAF activity. We compared the effects of doxepin on PAF-induced intradermal responses with those of terfenadine and cimetidine in this study.
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PMID:Effects of H1- and H2-antihistamines on platelet-activating factor and bradykinin-induced inflammatory responses in human skin. 868 66

Angiotensin-converting enzyme (ACE) inhibitor associated angioedema was detected in 39 subjects (17%) of 231 consecutive patients examined in the last 5 years at our out-patient clinic for symptoms of angioedema without urticaria. In these patients, angioedema was most commonly localized to the face. The duration of ACE-inhibitor treatment at the onset of angioedema ranged from 1 day to 8 years with a median of 6 months. The time elapsed between onset of angioedema and withdrawal of ACE-inhibitor ranged from 1 day to 10 years with a median of 10 months. Delayed diagnosis is explained by the unusual characteristics of this adverse reaction: angioedema may start years after beginning the treatment and then it recurs irregularly. In fact, ACE-inhibitors seem to facilitate angioedema in predisposed subjects, rather than causing it with an allergic or idiosyncratic mechanism. Thus, while Cl-inhibitor levels are usually normal in subjects developing ACE-inhibitor-dependent angioedema, we found that ACE-inhibitors caused angioedema in Cl-inhibitor-deficient patients. Because the main inactivator of bradykinin is kininase II, which is identical with ACE, it is believed that bradykinin mediates ACE-inhibitor-dependent angioedema. We had the possibility to examine the plasma bradykinin levels in one ACE-inhibitor-treated patient during an angioedema attack and we found very high levels, but we did not find an increase of break-down products of high-molecular-weight-kininogen as observed during acute attacks in hereditary angioedema. Bradykinin fell to normal levels during remission after withdrawal of the drug. These observations indicate that in ACE-inhibitor-induced angioedema, contrary to hereditary angioedema, the reduction of bradykinin catabolic rate plays a predominant role.
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PMID:Angioedema due to angiotensin-converting enzyme inhibitors. 1060 20

Congenital C1-inhibitor deficiency, or hereditary angioneurotic edema (HAE), is a rare autosomal dominant disease due to alterations in the C1 inhibitor gene that results in a deficiency of antigenic and/or functional C1-INH. Affected patients are heterozygous, and their deficiency is incomplete, many of them having up to 20% of the normal amount of the inhibitor. The disease is characterised by recurrent, circumscribed, non-pitting, and non-pruritic subepithelial swellings of sudden onset, which fade during the course of 48-72 hours, but can persist up to 1 week. Lesions can be solitary or multiple and primarily involve the extremities, larynx, face, and bowel wall. Bradykinin is believed to be the main, but certainly not the sole, mediator responsible for the bouts of edema in HAE. The diagnosis is suggested by family history, the lack of accompanying pruritus or urticaria, the presence of recurrent gastrointestinal attacks of colics, and episodes of laryngeal edema. Diminished C4 concentrations during symptomatic periods are highly suggestive for the diagnosis. Further laboratory diagnosis depends on demonstrating a deficiency of C1-INH antigen (type I) in most kindreds, but some kindreds have an antigenically intact but dysfunctional protein (type II) and require a functional assay to establish the diagnosis. Prophylactic administration of either attenuated androgens or protease inhibitors has proved useful in reducing frequency or severity of attacks. Infusions of a vapour-heated C1-INH concentrate are safe and effective means of both preventing and treating attacks. Nevertheless, this treatment is expensive and this extract is not readily available. It is emphasised that administration of angiotensin converting enzyme inhibitors is contraindicated in patients suffering from protease inhibitor deficiency states.
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PMID:Hereditary angioneurotic edema: review of the literature. 1078 4

Angioedema is a frequent disorder with multiple aetiologies. Angioedemas associated with urticaria are usually caused by histamine release and respond to anti-histamines and adrenalin. They include allergic angioedemas, anaphylactoid reactions (mostly drug-induced, e.g. NSAID), physical angioedemas and recurrent idiopathic angioedema. Bradykinin probably plays a causative role in the pathogenesis of ACE-inhibitor or angiotensin II receptor blocker related angioedemas, as well as in the pathogenesis of the rare hereditary or acquired C1-inhibitor deficiency angioedemas. Urticaria is then typically absent and anti-histamines, as well as adrenalin, are ineffective.
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PMID:[The multiple etiologies of angioedema]. 1855 32

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 edema or tongue/pharyngeal edema that obstructs the airway) is seen in anaphylactic/anaphylactoid reactions and the disorders mediated by bradykinin.
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PMID:Angioedema. 2328 6

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.
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PMID:Non-histaminergic angioedema: focus on bradykinin-mediated angioedema. 2351 34

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.
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PMID:[Bradykinin-induced angioedema: Definition, pathogenesis, clinical presentation, diagnosis and therapy]. 2659 36

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.
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PMID:Bradykinin-mediated angioedema. 2684 79

Angioedema is an acute swelling of the deeper layers of the skin or mucosa resulting from a transient increase in vascular permeability. Angioedema can occur in the absence or presence of hives, be hereditary or acquired, and be caused by various potential mediators, including histamine and bradykinin. Bradykinin-mediated angioedema can be difficult to diagnose but is responsible for a disproportionate percentage of the serious morbidity and mortality associated with angioedema. Our understanding of the basic biology of angioedema has dramatically expanded over recent years. The classification of angioedema has correspondently undergone major changes. Optimal management of patients with angioedema requires that an accurate diagnosis be established and that treatment be tailored to the patient's specific form of angioedema. In this article, we review the biology of bradykinin-mediated angioedema as well as the clinical approach to the evaluation of angioedema with a focus on bradykinin-mediated angioedema. Recognizing how the underlying pathophysiology and mechanisms of bradykinin dysregulation contribute to angioedema can help guide the clinical approach to the patient.
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PMID:Angioedema Due to Bradykinin Dysregulation. 3003 14

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. Bradykinin-induced angioedema is not associated with urticaria or other symptoms of type I hypersensitivity reactions. For many of the known triggers of angioedema, the mechanism is unclear. While mast cell and bradykinin-mediated angioedema are relatively well defined in terms of diagnostic and therapeutic approach, angioedema with unknown mechanisms represents a challenge for patients and clinicians alike. Elucidating the clinical pattern and the possible causes of isolated angioedema is the key to a correct diagnosis. This review summarizes the causes, and clinical features of angioedema, with a focus on isolated angioedema.
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PMID:Isolated angioedema: An overview of clinical features and etiology. 3067 75


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