Materiały źródłowe

• #1 Urticaria and Angioedema – Clinical Methods – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK209/

  Urticaria and angioedema are common patterns of reaction to a wide variety of stimuli acting through different mechanisms. The final common pathway is vasodilation, increased vascular permeability, and tissue edema. Immediate hypersensitivity involving the binding of IgE molecules to receptors on tissue mast cells is responsible for true allergic reactions. […] Hereditary angioedema is associated with a deficiency of C1 esterase inhibitor, a serum protein that not only inhibits the activated first component of complement but also blocks the fibrinolytic enzyme plasmin, activated Hageman factor, and kallikrein. Minor trauma, which can activate Hageman factor, often precipitates attacks. Activation of Hageman factor may be the initiating event leading to the generation of vasoactive substances from a complex interaction of the coagulation, fibrinolytic, kinin, and complement systems. […] For most cases of chronic urticaria and angioedema, the etiology and pathogenic mechanisms remain unknown. In some entities, such as cholinergic urticaria, the pathogenic mechanism is unknown even though the inciting stimulus may be clearly defined.

• #1 Urticaria and angioedema | Allergy, Asthma & Clinical Immunology | Full Text

  https://aacijournal.biomedcentral.com/articles/10.1186/s13223-018-0288-z

  Urticaria (hives) is a common disorder that often presents with angioedema (swelling that occurs beneath the skin). […] Angioedema can occur in the absence of urticaria and can be broadly divided into histamine-mediated and non-histamine-mediated angioedema. Histamine-mediated angioedema can be allergic, pseudoallergic or idiopathic. Non-histamine mediated angioedema is largely driven by bradykinin and can be hereditary, acquired or drug-induced, such as with angiotensin-converting enzyme inhibitors. […] Mast cells are the primary effector cells in urticaria and in many cases of angioedema. These cells are widely distributed in the skin, mucosa, and other areas of the body, and have high-affinity immunoglobulin E (IgE) receptors. Mast cell degranulation leads to the rapid release of various inflammatory mediators, such as histamine, leukotrienes and prostaglandins, which, in turn, cause vasodilation and leakage of plasma in and below the skin.

• #1 Urticaria: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/762917-overview

  Urticaria (hives) results from the release of histamine, bradykinin, leukotriene C4, prostaglandin D2, and other vasoactive substances from mast cells and basophils in the dermis. […] The activation of the H1 histamine receptors on endothelial and smooth muscle cells leads to increased capillary permeability. The activation of the H2 histamine receptors leads to arteriolar and venule vasodilation. […] The type I allergic IgE response is initiated by antigen-mediated IgE immune complexes that bind and cross-link Fc receptors on the surface of mast cells and basophils, thus causing degranulation with histamine release. The type II allergic response is mediated by cytotoxic T cells, causing deposits of immunoglobulins, complement, and fibrin around blood vessels. This leads to urticarial vasculitis. The type III immune-complex disease is associated with systemic lupus erythematosus and other autoimmune diseases that cause urticaria.

• #1 Urticaria – Dermatologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/dermatologic-disorders/approach-to-the-dermatologic-patient/urticaria

  Urticaria also may be accompanied by angioedema, which results from mast cell and basophil activation in the deeper dermis and subcutaneous tissues and manifests as edema of the face and lips, extremities, or genitals. Angioedema can occur in the bowel and manifest as colicky abdominal pain. Angioedema can be life-threatening if airway obstruction occurs because of laryngeal edema or tongue swelling. […] Urticaria results from the release of histamine, bradykinin, kallikrein, and other vasoactive substances from mast cells and basophils in the superficial dermis, resulting in intradermal edema caused by capillary and venous vasodilation and occasionally caused by leukocyte infiltration. […] The process can be immune mediated or nonimmune mediated. […] Immune-mediated mast cell activation includes Type I hypersensitivity reactions, in which allergen-bound IgE antibodies bind to high-affinity cell surface receptors on mast cells and basophils.

• #1 Urticaria: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/762917-overview

  Certain drugs (opioids, vecuronium, succinylcholine, vancomycin, and others) as well as radiocontrast agents cause urticaria due to mast cell degranulation through a nonIgE-mediated mechanism. […] For some urticarias, especially chronic urticarias, no cause can be found, despite exhaustive efforts—the so-called idiopathic urticarias, although most of these are chronic autoimmune urticaria as defined by a positive autologous serum skin test (ASST). […] To date, no reliable test exists to identify with certainty if chronic urticaria is autoimmune or nonautoimmune in the specific patient.

• #1 Urticaria and Angioedema: Understanding Complex Pathomechanisms to Facilitate Patient Communication, Disease Management, and Future Treatment – PubMed

  https://pubmed.ncbi.nlm.nih.gov/36610760/

  Chronic spontaneous urticaria (CSU) is primarily a T2-dominant disease with a complex genetic background. Skin mast cell activation can be induced not only via the IgE-FcRI axis but also from several other distinct mechanisms, molecules, and receptors involved in CSU onset, persistence, and exacerbation. […] The cornerstone of angioedema (AE) pathogenesis is increased vascular permeability and plasma leakage into the deeper dermis and subcutis, either mediated by histamine or bradykinin (BK). C1-inhibitor deficiency, hereditary or acquired, is the primary cause of BK-mediated AE due to increased plasma BK concentration. Other complex conditions have been identified, with some likely involving contact system dysregulation and other putative mechanisms related to vascular endothelial dysfunction.

• #1 Chronic Urticaria—Pathogenesis, Diagnostics, Therapy and Influence of Coexisting Angioedema

  https://www.mdpi.com/2077-0383/12/2/688

  Urticaria is one of the most frequent dermatological diseases and it usually occurs in paroxysmal, recurrent form. Urticarial wheal is a visible edema of the skin, which is caused by the increased permeability of blood vessels. The most important role in the pathogenesis of this disease is played by histamine, which is released from mast cells. Immune mechanisms depend on IgE and its complement system. Non-immunological mechanisms, including the direct degranulation of mast cells, play a significant role as well. In about one third of patients diagnosed with chronic urticaria, IgG auto-antibodies to IgE or to IgE high-affinity receptors occur. […] Currently, two endotypes of CSU can be distinguished, which vary in terms of pathogenesis and markers of the disease, as well as clinical course and sensitivity to treatment applied: type I and IIb. Type I CSU is related to the occurrence of IgE antibodies to autoantigens such as TPO (thyroid peroxidase), TG (thyroglobulin), ds-DNA (double-stranded DNA) and Il-24. In type I, it is observed that the occurrence of allergic diseases and the total concentration of IgE are normal or even increased. In type IIb CSU, IgG and IgM antibodies to IgE and high-affinity receptors for IgE (FceRI) are identified. Additionally, in the clinical course of this endotype, greater severity of symptoms and a prolonged duration of the disease, coexistence of autoimmune diseases, presence of ANA (antinuclear antibodies), elevated CRP levels, basopenia and eosinopenia in peripheral blood and reduced levels of total IgE occur.

• #1 Urticaria and Angioedema | Obgyn Key

  https://obgynkey.com/urticaria-and-angioedema/

  Urticaria is characterized by the waxing and waning appearance of pruritic, erythematous papules or plaques with superficial swelling of the dermis. […] The swelling observed with urticaria and angioedema results from the movement of plasma from small blood vessels into adjacent connective tissue. […] Unlike atopic dermatitis, the pruritus of urticaria is driven by histamine. […] The pathogenesis of CIU is still unknown, although autoantibodies and cells typically involved in IgE-mediated reactions, such as mast cells and basophils, have been implicated. […] About 30% to 40% of patients with CIU are classified as having autoimmune urticaria, a subgroup of CIU defined by the presence of histamine-releasing autoantibodies. […] The majority of these autoantibodies are directed against the subunit of the high-affinity receptor, FcRI; the remainder target IgE.

• #1 Urticaria and Angioedema | Obgyn Key

  https://obgynkey.com/urticaria-and-angioedema/

  Injection of autologous serum, also known as the autologous serum skin test (ASST), leads to a wheal-and-flare response in CIU patients, suggesting that the causative agent is in the serum. […] More recently, the role of mast cells and basophils has been investigated. […] Skin biopsies of patients with CIU demonstrate mast cell degranulation accompanied by increased mast cell releasibility that reverses with disease remission. […] Basophils, which typically are not present in the skin, are observed in both lesional and nonlesional CIU skin biopsies. […] Angioedema, which is a swelling of the dermis, subcutaneous, and submucosal tissues, often coexists with urticaria but typically persists past 24 hours. […] The lack of pruritus in angioedema may be caused by fewer mast cells in the lower dermis and subcutis.

• #1 Urticaria | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-022-00389-z

  Urticaria is an inflammatory skin disorder that affects up to 20% of the world population at some point during their life. It presents with wheals, angioedema or both due to activation and degranulation of skin mast cells and the release of histamine and other mediators. […] The pathogenesis of CSU consists of several interlinked events involving autoantibodies, complement and coagulation. […] In this study, IL-24 is a common, specific and functional autoantigen of IgE antibodies in patients with CSU, suggesting autoallergic mechanism in many patients with CSU. […] The role of coagulation and complement factors for mast cell activation in the pathogenesis of chronic spontaneous urticaria. […] Coagulation factors induce human skin mast cell and basophil degranulation via activation of complement 5 and the C5a receptor.

• #1 Urticaria – Kaplan AP (Updated 2019)

  https://www.worldallergy.org/component/content/article/urticaria-kaplan-ap-updated-2019?catid=16&Itemid=101

  This type of urticaria is a self-limiting process that occurs when mast cells in the skin are activated, degranulate, and secrete histamine, leukotrienes, platelet activating factor (PAF), enzymes such as tryptase and chymase, cytokines, and chemotactic cytokines (chemokines). […] If an allergic reaction causes hives or swelling, it is usually ingested (food, oral drug) or injected (drugs, stings). […] Acute urticaria can result from „non-specific” stimulation of mast cells, when there is degranulation of mast cells in the absence of a defined allergen. […] Urticaria and angioedema can result from agents that alter the metabolism of arachidonic acid, such as aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). […] Chronic spontaneous urticaria is characterized by a non-necrotizing perivascular mononuclear-cell infiltrate (CD4 positive T lymphocytes and monocytes) with variable accumulation of eosinophils, neutrophils, and mast cells.

• #1 Angioedema: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/135208-overview

  Plasma and tissue factors, such as bradykinin, and certain components in the contact system or the fibrinolytic system are also found to play an important role in certain forms of angioedema. […] For angioedema without evidence of histamine involvement, bradykinin is likely the most important mediator. […] C1-INH is a serine protease that is involved in the regulation of bradykinin, a potent vasoactive substance. Low levels of this protease (either hereditary or acquired) results in unchecked activation of the kallikrein-kinin system, which leads to the overproduction of bradykinin. […] Besides mast cells, many other cellular components (eg, macrophages, dendritic cells, lymphocytes, monocytes, eosinophils, and endothelial cells) are involved in the pathogenesis of angioedema. […] Angioedema associated with urticaria may represent hypersensitivity to an offending agent. Histamine is released into the bloodstream, resulting in increased endothelial cell permeability.

• #1 Angioedema: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/135208-overview

  Angioedema is a result of the fast onset of an increase in local vascular permeability in subcutaneous or submucosal tissue. Histamine and bradykinin are the most recognized vasoactive mediators known to be critical in the pathologic process of angioedema; most cases of angioedema are primarily mediated by 1 of these 2 mediators, though some investigators indicate the possibility that both may be involved in certain cases. […] Other vasoactive mediators are, at least in part, involved in the pathogenesis of various types of angioedema. Leukotrienes, for example, may play an important role in the onset of angioedema that is induced by nonsteroidal anti-inflammatory drugs (NSAIDs). […] For histamine-mediated angioedema (histaminergic angioedema), mast cells and basophils are the primary sources of histamine. The activation of mast cells or basophils with subsequent histamine release may be either mediated or unmediated by immunoglobulin E (IgE).

• #1 Angioedema – Immunology; Allergic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/angioedema

  Acute angioedema is mast cell-mediated in 90% of cases. […] Angiotensin-converting enzyme (ACE) inhibitors cause about 30% of cases of acute angioedema seen in emergency departments. ACE inhibitors can directly increase levels of bradykinin. […] The cause of chronic (6 weeks) angioedema is usually unknown. […] Hereditary angioedema and acquired angioedema are disorders that are characterized by abnormal complement responses and caused by deficiency or dysfunction of C1 inhibitor. Symptoms are those of bradykinin-mediated angioedema. […] In the emergency department, about 30% of cases of acute angioedema are caused by angiotensin-converting enzyme (ACE) inhibitors (bradykinin-mediated), although overall, 90% of cases are mast cell-mediated. […] Swelling always develops; bradykinin-mediated angioedema tends to develop more slowly and to cause fewer symptoms of an acute allergic reaction (eg, pruritus, urticaria, anaphylactic shock) than does mast cell-mediated angioedema.

• #1 Angioedema – Wikipedia

  https://en.wikipedia.org/wiki/Angioedema

  The underlying mechanism typically involves histamine or bradykinin. […] In hereditary angioedema, bradykinin plays a critical role in all forms of the condition. […] Various mechanisms that interfere with bradykinin production or degradation can lead to angioedema. […] In hereditary angioedema, bradykinin formation is caused by continuous activation of the complement system due to a deficiency in one of its prime inhibitors, C1-esterase. […] The pathogenesis of hereditary angioedema is suspected to be related to unopposed activation of the contact pathway by the initial generation of kallikrein and/or clotting factor XII by damaged endothelial cells. […] The end product of this cascade, bradykinin, is produced in large amounts and is believed to be the predominant mediator leading to increased vascular permeability and vasodilation that induces typical angioedema „attacks”.

• #1 Angioedema – Kaplan A (Updated 2019)

  https://www.worldallergy.org/component/content/article/angioedema-kaplan-a-updated-2019?catid=16&Itemid=101

  Angioedema is a transient swelling of the skin or submucosal surface due to increased vascular permeability of small venules. […] When urticaria and angioedema are present concomitantly, the cause can be considered to be the result of cutaneous mast cell degranulation with release of histamine, leucotrienes, cytokines, and chemokines. […] Although urticaria accompanies angioedema in most instances, angioedema can be seen without urticaria yet the cause and pathogenic mechanism(s) are the same. […] The swelling characteristic of C1 inhibition is caused by over production of bradykinin. […] C1 INH inhibits two of the plasma enzymes requisite for bradykinin formation; namely, activated factor XII and plasma kallikrein as depicted in Fig. 2. […] Bradykinin causes angioedema by stimulating contractile elements in endothelial cells so as to create spaces (pores) between the cells through which fluid can pass.

• #1 Angioedema – Immunology; Allergic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/immunology-allergic-disorders/allergic-autoimmune-and-other-hypersensitivity-disorders/angioedema

  Angioedema is edema of the deep dermis and subcutaneous tissues. […] Angioedema can also be a hereditary or an acquired disorder characterized by an abnormal complement response. The main symptom is swelling, often of the face, mouth, and upper airways, which can be severe. […] Angioedema is swelling (usually localized) of the subcutaneous tissues due to increased vascular permeability and extravasation of intravascular fluid. Known mediators of increased vascular permeability include the following: Mast cell-derived mediators (eg, histamine, leukotrienes, prostaglandins) […] Bradykinin and complement-derived mediators. […] In bradykinin-mediated angioedema, the dermis is usually spared, so urticaria and pruritus are absent. […] Several causes (eg, calcium channel blockers, fibrinolytic agents) have no identified mechanism; sometimes a cause (eg, muscle relaxants) with a known mechanism is overlooked clinically.

• #1

  https://link.springer.com/article/10.1007/s13671-013-0061-y

  Urticaria and angioedema occur in up to 20 % of the population during their lifetime. Chronic urticaria and some hereditary angioedema states are more frequent in women and fluctuate during the hormonal cycle. […] The pathogenesis of urticarial lesions is degranulation of mast cells and the release of vasoactive substances, the most important of which is histamine. This process is mediated by immunoglobulin E (IgE) binding to the Fc receptor on mast cells. Other physical, chemical, and hormonal factors may lead to spontaneous degranulation of mast cells, not through an antigen-antibody mechanism. […] The pathogenesis of HAE includes either deficiency (type I) or malfunction (type II) of C1 esterase inhibitor (C1EI), which is a key enzyme in three different pathways: the coagulation/fibrinolysis pathway, in which it inhibits factor XII, factor XI, and plasmin; the classic complement system, in which it inhibits the action of C1s and C1r, preventing overactivation of the complement cascade; the contact system, in which it inhibits the enzyme kallikrein, which forms bradykinin from high molecular weight kininogen.

• #1 Angioedema | World Allergy Organization Journal | Full Text

  https://waojournal.biomedcentral.com/articles/10.1097/WOX.0b013e31817aecbe

  With ACE inhibition, bradykinin accumulates and interacts with vascular B-2 receptors to cause vasodilation and to increase vascular permeability, with a concomitant increase in cyclic guanosine monophosphate and release of nitric oxide. […] The disease was first demonstrated by Virginia Donaldson to be caused by a defect in the serpin (serine protease inhibitor) C1 INH. […] This deficiency causes an abnormal increase in activation of C1, leading to consumption of C2 and C4 and correspondingly low plasma levels of these proteins. […] It also causes excessive formation of the enzyme kallikrein, resulting in increased transformation of kininogen to kinins including the highly vasoactive nonapeptide bradykinin. […] The evidence is now substantiated that bradykinin is the cause of the swelling rather than any vasoactive peptide resulting from complement activation.

• #1 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Angioedema-Pathophysiology.aspx

  Pathogenesis of the types of angioedema has been studied extensively. […] Evidence shows that there is a C1 esterase inhibitor (C1 INH) deficiency. Normally C1 INH is responsible for regulation of activity of inflammatory mediators like complement component C1. Activation of C1 is the first step in the activation of complements and their role in inflammation. […] If there is a deficiency of C1 INH the mediators of inflammation like bradykinin, kallikrein, and plasmin become overtly active. […] Acquired angioedema also results due to C1 INH deficiency. There are 2 types of acquired angioedema and both have autoimmune mechanisms in their pathology. […] Angiotensin-Converting Enzyme Inhibitors or ACE inhibitors are one of the common drugs that cause angioedemas. This results mainly due to raised levels of bradykinins. […] In these conditions there is a raised level of several cytokines. There is an increased level of the cytokines granulocyte-macrophage colony-stimulating factor, interleukin (IL)-3, IL-5, and IL-6.

• #1 Angioedema – Kaplan A (Updated 2019)

  https://www.worldallergy.org/component/content/article/angioedema-kaplan-a-updated-2019?catid=16&Itemid=101

  This disorder is due to IgG antibody to C1 INH (present in close to 90% of patients) thus it is an autoimmune disorder. […] The C4 is low, like HAE with C1 INH deficiency and quantitation of C1 INH by protein or function is greatly diminished. […] This is the most common form of angioedema seen in emergency rooms and is presumed (but not proven) to be caused by bradykinin accumulation. […] Therapy can be divided into approaches that deal with interrupting an acute episode vs those administered prophylactically to prevent attacks of swelling. […] The antifibrinolytic agent tranexamic acid may be particularly useful in the treatment of HAE with factor XII mutation since it is particularly susceptible to activation by plasmin. […] Treatment of ACE inhibitor angioedema is to avoid all ACE inhibitor preparations.

• #1 Clinical Practice Guideline: Initial Evaluation and Management of Patients Presenting with Acute Urticaria or Angioedema – AAEM

  https://www.aaem.org/statements/clinical-practice-guideline-initial-evaluation-and-management-of-patients-presenting-with-acute-urticaria-or-angioedema/

  Degranulation of mast cells by circulating auto-antibodies defines autoimmune-mediated urticaria. […] Angioedema commonly accompanies urticaria. […] There is no fundamental difference between the lesions of urticaria and angioedema. […] Both result from local vasodilatation and increased vascular permeability. […] Etiologies of angioedema are divided into mast cell mediated and non-mast cell mediated. […] The mechanisms are identical to that of isolated urticaria and are discussed above. […] The two most common mechanisms of non-mast cell mediated angioedema are abnormalities in the bradykinin pathway and abnormalities of the complement system. […] The pathophysiology of ACE inhibitor angioedema remains controversial. […] Most theories center on the decreased degradation of bradykinin, a potent vasodilator that increases vascular permeability. […] It is likely that other humoral factors such as nitric oxide, interleukin-1, and tumor necrosis factor are involved. […] Defects in C1INH, carboxyalkyldipeptide N, and urinary kallikrein have also been proposed as mechanisms for ACE inhibitor angioedema.

• #1 Urticaria and Angioedema: A Practical Approach | AAFP

  https://www.aafp.org/pubs/afp/issues/2004/0301/p1123.html

  Urticaria also has been associated with herpes virus, cytomegalovirus, Epstein-Barr virus, and chronic hepatitis infections, and with bacterial, fungal, and parasitic infections. […] Urticarial vasculitis should be considered if a single urticaria lesion lasts longer than 24 hours, if lesions are burning or painful, if they are more common in the lower extremities, and if they leave an area of hemosiderin pigment after they have resolved. […] Ingestion of certain foods, including strawberries, tomatoes, shrimp, lobster, cheese, spinach, and eggplant, also can trigger hives through direct mast cell degranulation. […] Angioedema has been reported in patients taking angiotensin-converting enzyme inhibitors. […] Patients with a rare inherited or acquired disorder linked to C1 esterase deficiency or autoimmune consumption may present with recurrent angioedema without urticaria.

• #1 The Role of Infection and Autoimmunity in Urticaria and Angioedema as a Common Entity – European Medical Journal

  https://www.emjreviews.com/allergy-immunology/article/the-role-of-infection-and-autoimmunity-in-urticaria-and-angioedema-as-a-common-entity-j010121/

  Histamine release likely occurs through cross-linking receptors by IgG-specific and specific auto-immune IgE autoantibodies derived against antigens, on mast cells and basophils. […] Autoimmune mechanisms are contributing to the pathogenesis of chronic urticaria; different pathogenic autoantibodies, causing a release of histamine after reaction with IgE epitopes, or with the -chain of Fc epsilon RI receptors, are considered. […] Urticaria may be accompanied by the presence of angioedema, which is a similar process that occurs at submucosal surfaces of the upper respiratory and gastrointestinal tracts and deeper layers of the skin including subcutaneous tissue. […] CSU is an inflammatory disorder with autoimmune features (termed chronic viral urticaria) based on serology, consistent with the hypothesis that reactivation of a latent human herpesvirus (HHV) or viruses may play a role in CSU. […] The author can hypothesise that the underlying lasting immune response to an infection, rather than infection itself, is the causative factor for persistence of urticaria, alongside autoimmune factors.

• #1

  https://link.springer.com/article/10.1007/s13671-013-0061-y

  Estrogen has been shown to affect the contact and coagulation systems by increasing the levels and function of factor XII, prekallikrein, kallikrein, and high molecular weight kininogen, all of which are involved in the process of bradykinin formation. Estrogens also up-regulate the expression and potentiate the activity of bradykinin receptor B2. […] The influence of progesterone on the course of HAE is inconclusive. It is known to raise the levels of kallikrein, thereby increasing bradykinin formation. […] The attack rate may increase, decrease, or remain the same during pregnancy. […] Estrogens were proved to reduce plasma C1-inhibitor levels and to increase the transcription of factor XII, plasma prekallikrein, and bradykinin 2 receptors. Estrogens also decrease the levels of ACE inhibitor, a key enzyme in the degradation of bradykinin.

• #1

  https://link.springer.com/article/10.1007/s13671-013-0061-y

  Estrogen and progesterone levels, which rise dramatically in pregnancy, probably play a role in at least some urticarial rashes and angioedema states. The influence of estrogens on bradykininergic angioedema of HAE type I/II is the most prominent, and they might aggravate the disease, especially in the first and last trimesters of pregnancy. […] Sex hormones might play some role in the pathogenesis of disease.

• #1 Urticaria and Angioedema | IntechOpen

  https://www.intechopen.com/chapters/54456

  Complement activation leading to release of C3a, C4a and C5a can stimulate mast cells. […] Non-immunemediated urticaria involves direct activation of mast cells by non-IgE mechanisms examples of which are physical stimuli, radiocontrast dyes, drugs, such as opiates and vancomycin. […] Autoimmune urticaria involves autoantibodies causing mast cell degranulation. […] As noted all mechanisms lead to activation of mast cells causing liberation of histamine, leukotriene C4 and prostaglandin D2. […] These vasoactive mediators cause vasodilatation and extravasation of plasma from postcapillary venules. […] In 45 hours, an inflammatory cytokine response including tumor necrosis factor, interleukin 4 and interleukin 5 recruits a perivascular inflammatory infiltrate. […] The result is the formation a pruritic urticarial plaque or angioedema.

• #1 Clinical Practice Guideline: Initial Evaluation and Management of Patients Presenting with Acute Urticaria or Angioedema – AAEM

  https://www.aaem.org/statements/clinical-practice-guideline-initial-evaluation-and-management-of-patients-presenting-with-acute-urticaria-or-angioedema/

  Mechanisms of urticaria can be classified into one of four categories: immune-mediated, complement-mediated, non-immune mediated, and autoimmune-mediated. […] Mast cell release of preformed mediators results in endothelial activation, vasodilatation, and increased vascular permeability. […] Vasoactive mediators implicated in urticaria include histamine, prostaglandin D2, cysteinyl leukotrienes C4 and D4, platelet activating factor, anaphylotoxins, histamine releasing factor, cytokines, and chemokines. […] Immune-mediated urticaria results from the cross-linking of IgE located on the surface of mast cells and basophils. […] Complement-mediated urticaria is caused by the direct activation of mast cells by complement proteins, most notably the anaphylatoxins C3a, C4a, and C5a. […] Non-immune mediated urticaria results from the direct activation of mast cells by non-IgE mechanisms.

• #1 Urticaria and angioedema — IRISH DERM TUTOR

  https://irishdermtutor.com/urticaria-and-angioedema

  Pathogenesis classification […] Based on pathogenesis: Immunologic, non-immunologic or inducible (eg physical) […] The mast cell is a cell that can be found predominantly in skin, submucosa and bowel mucosa. Histamine is produced and stored in the mast cell in granules and is the most important mediator of urticaria. Urticaria results from mast cell (+ basophil) degranulation which leads to the release of preformed vasoactive mediators (eg histamine and others such as tryptase). Get symptoms and signs due to the resulting vasodilation, increased blood flow and increased vascular permeability. Following the initial release of preformed mediators mast cells and other cells (eg eosinophils, neutrophils) make and release secondary mediators like prostaglandins (cyclo-oxygenase enzyme pathway) and leukotrines (lipoxygenase pathway) which are derived from arachidonic acid and further contribute to the symptoms and signs. Angioedema involves additional mechanisms such as bradykinin release and as such antihistamines may not be as effective. There are a variety of immunologic, non immunologic, physical and chemical stimuli that can cause urticaria. Angioedema without weals can be seen in conditions where bradykinin is increased. Going into the immunological mechanisms in more detail, this can be related to the adaptive (allergic, autoimmune, immune complex formation) or the innate immune system (autoinflammatory syndromes). Approximately 33% of people with chronic spontaneous urticaria have functional histamine-releasing IgG autoantibodies. This subgroup of patients may have a more intense and protracted disease course. An antibody and antigen form an immune complex which can trigger the complement pathway. This can lead to increase in C5a (anaphylotoxin) which causes mast cell degranulation. Get dysregulation of innate immunity leading to persistent uncontrolled inflammation in the absence of an identifiable trigger. Get excessive cytokine production which can lead to urticaria.

• #1 Angioedema: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/135208-overview

  With respect to pathophysiology, angioedema without urticaria may differ substantially from angioedema with urticaria. In many cases, histamine is not involved or only minimally involved. Bradykinin is known to be the major mediator for HAE, acquired angioedema (AAE), ACE inhibitor-induced angioedema, and certain idiopathic angioedemas.

• #1 Urticaria and angioedema | Allergy, Asthma & Clinical Immunology | Full Text

  https://aacijournal.biomedcentral.com/articles/10.1186/s13223-018-0288-z

  Although the exact pathogenesis of attacks of HAE and AAE remains unclear, excess production of the potent vasodilatory peptide, bradykinin (which is regulated by the C1-INH), appears to play an important role. […] It is important to note that histamine and other mast cell mediators that are typical of urticaria and associated angioedema are not directly involved in HAE and AAE, which explains patient lack of response to antihistamines and corticosteroids, and distinguishes these forms of isolated angioedema from that associated with urticaria. […] In the case of HAE, AAE or ACE inhibitor-induced angioedema, the vasodilatory peptide, bradykinin, plays a key role in endothelial cell activation, with resultant tissue edema. Bradykinin is released from many cell types, and mechanisms that interfere in either its production or as in the case of ACE inhibitors its degradation, result in angioedema.

• #2 Urticaria and angioedema | Allergy, Asthma & Clinical Immunology | Full Text

  https://aacijournal.biomedcentral.com/articles/10.1186/s13223-018-0288-z

  Urticaria (hives) is a common disorder that often presents with angioedema (swelling that occurs beneath the skin). […] Angioedema can occur in the absence of urticaria and can be broadly divided into histamine-mediated and non-histamine-mediated angioedema. Histamine-mediated angioedema can be allergic, pseudoallergic or idiopathic. Non-histamine mediated angioedema is largely driven by bradykinin and can be hereditary, acquired or drug-induced, such as with angiotensin-converting enzyme inhibitors. […] Mast cells are the primary effector cells in urticaria and in many cases of angioedema. These cells are widely distributed in the skin, mucosa, and other areas of the body, and have high-affinity immunoglobulin E (IgE) receptors. Mast cell degranulation leads to the rapid release of various inflammatory mediators, such as histamine, leukotrienes and prostaglandins, which, in turn, cause vasodilation and leakage of plasma in and below the skin.

• #2 Urticaria: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/762917-overview

  Urticaria (hives) results from the release of histamine, bradykinin, leukotriene C4, prostaglandin D2, and other vasoactive substances from mast cells and basophils in the dermis. […] The activation of the H1 histamine receptors on endothelial and smooth muscle cells leads to increased capillary permeability. The activation of the H2 histamine receptors leads to arteriolar and venule vasodilation. […] The type I allergic IgE response is initiated by antigen-mediated IgE immune complexes that bind and cross-link Fc receptors on the surface of mast cells and basophils, thus causing degranulation with histamine release. The type II allergic response is mediated by cytotoxic T cells, causing deposits of immunoglobulins, complement, and fibrin around blood vessels. This leads to urticarial vasculitis. The type III immune-complex disease is associated with systemic lupus erythematosus and other autoimmune diseases that cause urticaria.

• #2 Urticaria – Kaplan AP (Updated 2019)

  https://www.worldallergy.org/component/content/article/urticaria-kaplan-ap-updated-2019?catid=16&Itemid=101

  This type of urticaria is a self-limiting process that occurs when mast cells in the skin are activated, degranulate, and secrete histamine, leukotrienes, platelet activating factor (PAF), enzymes such as tryptase and chymase, cytokines, and chemotactic cytokines (chemokines). […] If an allergic reaction causes hives or swelling, it is usually ingested (food, oral drug) or injected (drugs, stings). […] Acute urticaria can result from „non-specific” stimulation of mast cells, when there is degranulation of mast cells in the absence of a defined allergen. […] Urticaria and angioedema can result from agents that alter the metabolism of arachidonic acid, such as aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). […] Chronic spontaneous urticaria is characterized by a non-necrotizing perivascular mononuclear-cell infiltrate (CD4 positive T lymphocytes and monocytes) with variable accumulation of eosinophils, neutrophils, and mast cells.

• #2 Clinical Practice Guideline: Initial Evaluation and Management of Patients Presenting with Acute Urticaria or Angioedema – AAEM

  https://www.aaem.org/statements/clinical-practice-guideline-initial-evaluation-and-management-of-patients-presenting-with-acute-urticaria-or-angioedema/

  Mechanisms of urticaria can be classified into one of four categories: immune-mediated, complement-mediated, non-immune mediated, and autoimmune-mediated. […] Mast cell release of preformed mediators results in endothelial activation, vasodilatation, and increased vascular permeability. […] Vasoactive mediators implicated in urticaria include histamine, prostaglandin D2, cysteinyl leukotrienes C4 and D4, platelet activating factor, anaphylotoxins, histamine releasing factor, cytokines, and chemokines. […] Immune-mediated urticaria results from the cross-linking of IgE located on the surface of mast cells and basophils. […] Complement-mediated urticaria is caused by the direct activation of mast cells by complement proteins, most notably the anaphylatoxins C3a, C4a, and C5a. […] Non-immune mediated urticaria results from the direct activation of mast cells by non-IgE mechanisms.

• #2 Urticaria – Dermatologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/dermatologic-disorders/approach-to-the-dermatologic-patient/urticaria

  Urticaria also may be accompanied by angioedema, which results from mast cell and basophil activation in the deeper dermis and subcutaneous tissues and manifests as edema of the face and lips, extremities, or genitals. Angioedema can occur in the bowel and manifest as colicky abdominal pain. Angioedema can be life-threatening if airway obstruction occurs because of laryngeal edema or tongue swelling. […] Urticaria results from the release of histamine, bradykinin, kallikrein, and other vasoactive substances from mast cells and basophils in the superficial dermis, resulting in intradermal edema caused by capillary and venous vasodilation and occasionally caused by leukocyte infiltration. […] The process can be immune mediated or nonimmune mediated. […] Immune-mediated mast cell activation includes Type I hypersensitivity reactions, in which allergen-bound IgE antibodies bind to high-affinity cell surface receptors on mast cells and basophils.

• #2 Urticaria – Dermatologic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/dermatologic-disorders/approach-to-the-dermatologic-patient/urticaria

  Autoimmune disorders, in which antibodies to an IgE receptor functionally cross-link IgE receptors and cause mast cell degranulation. […] Nonimmune-mediated mast cell activation includes direct nonallergic activation of mast cells by certain medications or substances. […] Drug-induced cyclooxygenase inhibition that activates mast cells by poorly understood mechanisms. […] Activation by physical or emotional stimuli; mechanism is poorly understood but possibly involves the release of neuropeptides that interact with mast cells. […] Most chronic urticaria is idiopathic. The next most common cause is an autoimmune disorder. The causative autoimmune disease is sometimes clinically apparent. Urticarial vasculitis sometimes is associated with systemic rheumatic diseases (particularly SLE or Sjgren syndrome). In urticarial vasculitis, urticaria is accompanied by findings of leukocytoclastic vasculitis on histopathology; it should be considered when the urticaria is painful rather than pruritic, lasts 48 hours, does not blanch, or is accompanied by vesicles or purpura. […] Patients who have angioedema involving the oropharynx or any involvement of the airway should receive subcutaneous epinephrine 0.3 mL of 1:1000 solution and be admitted to the hospital.

• #2 Urticaria | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-022-00389-z

  Urticaria is an inflammatory skin disorder that affects up to 20% of the world population at some point during their life. It presents with wheals, angioedema or both due to activation and degranulation of skin mast cells and the release of histamine and other mediators. […] The pathogenesis of CSU consists of several interlinked events involving autoantibodies, complement and coagulation. […] In this study, IL-24 is a common, specific and functional autoantigen of IgE antibodies in patients with CSU, suggesting autoallergic mechanism in many patients with CSU. […] The role of coagulation and complement factors for mast cell activation in the pathogenesis of chronic spontaneous urticaria. […] Coagulation factors induce human skin mast cell and basophil degranulation via activation of complement 5 and the C5a receptor.

• #2 Immunology – What is urticaria and angioedema? :: Northern Care Alliance

  https://www.northerncarealliance.nhs.uk/patient-information/patient-leaflets/immunology-what-urticaria-and-angioedema

  Urticaria and angioedema are caused by the release of various substances, in particular a chemical in the body called histamine. Histamine causes blood vessels to leak and allow the clear liquid part of the blood to pass into the tissues, causing them to become swollen. Hives occur when histamine is released in superficial layers of the skin, and swelling occurs when histamine is released in the deeper tissues of the skin. […] In chronic urticaria and angioedema, the histamine packages are unstable and release histamine easily with no clear trigger. There are some factors which may contribute to the histamine release described in the next section. […] In some cases, this condition is thought to be caused by an autoimmune response. This means that there is a tendency in your immune system to cause some of the symptoms described above. […] In most cases an allergic mechanism is rarely the cause of the rash and swellings. […] Spontaneous CSU and angioedema is diagnosed when triggers have been excluded. Often the symptoms occur with no pattern, relationship or obvious outside trigger.

• #2

  https://link.springer.com/article/10.1007/s12016-017-8628-1

  Urticaria is a common, mast cell-driven disease presenting with wheals or angioedema or both. […] However, the pathogenesis is incompletely understood. […] Recent research focused on characterizing the role of cells and mediators involved in the pathogenesis of urticaria, identifying the mechanisms of mast cell activation, and investigating underlying autoimmune processes in chronic spontaneous urticaria. […] Novel therapeutic strategies aim at specifically targeting cells and mediators involved in the pathogenesis of urticaria. […] Mechanisms of action that contribute to efficacy of omalizumab in chronic spontaneous urticaria. […] The correlation of serum CCL11, CCL17, CCL26, and CCL27 and disease severity in patients with urticaria. […] Activation of the tissue factor pathway of blood coagulation in patients with chronic urticaria.

• #2 Urticaria & Angioedema | AMBOSS Rotation Prep

  https://resident360.amboss.com/adult-medicine/allergy-immunology/urticaria-angioedema/urticaria-angioedema.html

  Urticaria (also known as hives) is characterized by severely pruritic raised, erythematous, circumscribed lesions resulting from mast cell activation and subsequent release of histamine and other vasoactive mediators that lead to increased vascular permeability of postcapillary venules and subsequent edema, erythema, and pruritus. […] CIU is associated with autoimmune disorders such as Hashimoto thyroiditis (autoimmune hypothyroidism); evidence suggests that the urticaria may be caused by autoantibodies directed against mast cells in the skin in about half of patients with CIU. […] Angioedema involves a similar process as urticaria but affects the deep dermis and subcutaneous tissue and leads to nonpitting swelling. Angioedema can be mast-cell-mediated or bradykinin-mediated. […] Hereditary angioedema (HAE) is an autosomal dominant disorder characterized by a deficiency or dysfunction of functional C1 esterase inhibitor (C1-INH) that leads to excessive production of the vasoactive mediator bradykinin. This causes episodic increases in vascular permeability and angioedema. […] C4 is the best test to screen for HAE because it is low at baseline in approximately 96% of patients and during most attacks (in 99% of patients). C1-INH functional and quantitative levels can help differentiate between type I and type II HAE.

• #3

  https://link.springer.com/article/10.1007/s12016-017-8628-1

  Urticaria is a common, mast cell-driven disease presenting with wheals or angioedema or both. […] However, the pathogenesis is incompletely understood. […] Recent research focused on characterizing the role of cells and mediators involved in the pathogenesis of urticaria, identifying the mechanisms of mast cell activation, and investigating underlying autoimmune processes in chronic spontaneous urticaria. […] Novel therapeutic strategies aim at specifically targeting cells and mediators involved in the pathogenesis of urticaria. […] Mechanisms of action that contribute to efficacy of omalizumab in chronic spontaneous urticaria. […] The correlation of serum CCL11, CCL17, CCL26, and CCL27 and disease severity in patients with urticaria. […] Activation of the tissue factor pathway of blood coagulation in patients with chronic urticaria.

• #3 Urticaria – Kaplan AP (Updated 2019)

  https://www.worldallergy.org/component/content/article/urticaria-kaplan-ap-updated-2019?catid=16&Itemid=101

  This type of urticaria is a self-limiting process that occurs when mast cells in the skin are activated, degranulate, and secrete histamine, leukotrienes, platelet activating factor (PAF), enzymes such as tryptase and chymase, cytokines, and chemotactic cytokines (chemokines). […] If an allergic reaction causes hives or swelling, it is usually ingested (food, oral drug) or injected (drugs, stings). […] Acute urticaria can result from „non-specific” stimulation of mast cells, when there is degranulation of mast cells in the absence of a defined allergen. […] Urticaria and angioedema can result from agents that alter the metabolism of arachidonic acid, such as aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs). […] Chronic spontaneous urticaria is characterized by a non-necrotizing perivascular mononuclear-cell infiltrate (CD4 positive T lymphocytes and monocytes) with variable accumulation of eosinophils, neutrophils, and mast cells.

• #3 Urticaria and Angioedema | IntechOpen

  https://www.intechopen.com/chapters/54456

  Complement activation leading to release of C3a, C4a and C5a can stimulate mast cells. […] Non-immunemediated urticaria involves direct activation of mast cells by non-IgE mechanisms examples of which are physical stimuli, radiocontrast dyes, drugs, such as opiates and vancomycin. […] Autoimmune urticaria involves autoantibodies causing mast cell degranulation. […] As noted all mechanisms lead to activation of mast cells causing liberation of histamine, leukotriene C4 and prostaglandin D2. […] These vasoactive mediators cause vasodilatation and extravasation of plasma from postcapillary venules. […] In 45 hours, an inflammatory cytokine response including tumor necrosis factor, interleukin 4 and interleukin 5 recruits a perivascular inflammatory infiltrate. […] The result is the formation a pruritic urticarial plaque or angioedema.

• #3 Urticaria and Angioedema | IntechOpen

  https://www.intechopen.com/chapters/54456

  Urticaria is a common mast cellmediated dermatosis presenting with pruritic erythematous superficial plaques also known as hives or wheals. […] Angioedema is an acute condition manifesting as localized edema affecting the skin and mucous membranes. […] There are two different mechanisms causing angioedema. The first is mast cell mediated and is considered to be part of the spectrum of spontaneous or inducible urticarias. […] The second is bradykinin-induced angioedema, as observed in the hereditary angioedema and angiotensin-converting enzyme (ACE) inhibitorinduced angioedema. […] Pathophysiological mechanisms leading to formation of urticaria and angioedema can be immune-mediated, complement-mediated, non-immunemediated and autoimmune-mediated. […] As in most cases of acute urticaria, immune-mediated urticaria is an IgE-mediated hypersensitivity reaction.

• #3

  https://link.springer.com/article/10.1007/s12016-017-8628-1

  Severe chronic urticaria is associated with elevated plasma levels of D-dimer. […] Coagulation/fibrinolysis and inflammation markers are associated with disease activity in patients with chronic urticaria. […] Antithyroid antibodies in chronic urticaria and angioedema. […] IgE mediated autoallergy against thyroid peroxidasea novel pathomechanism of chronic spontaneous urticaria?

• #4 The Role of Infection and Autoimmunity in Urticaria and Angioedema as a Common Entity – European Medical Journal

  https://www.emjreviews.com/allergy-immunology/article/the-role-of-infection-and-autoimmunity-in-urticaria-and-angioedema-as-a-common-entity-j010121/

  Chronic spontaneous urticaria with angioedema is prevalent, affecting approximately 1% of the general population, and has a significant impact on quality of life, according to epidemiological data. […] Although chronic spontaneous urticaria with angioedema is a multifactorial condition involving inflammation, autoimmunity, and coagulation, IgE-mediated autoimmunity, or autoallergy, is thought to play a major role. […] It is understood that the underlying mechanism of urticaria is caused by activation of mast cells and basophils, which release pro-inflammatory mediators that result in increased permeability of blood vessels and irritation of nerve endings, leading to swelling and pruritus. […] Current research in chronic spontaneous urticaria (CSU) targets the role of cells and released mediators that lead to the development of urticaria through mast cell activation, with a focus on the underlying autoimmune processes.

Zobacz więcej