Angioedema
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The document discusses angioedema, including its definition as transient swelling in deep dermis or subcutaneous tissue resulting from vascular leakage. It outlines the pathophysiology of angioedema involving mast cell activation and the kallikrein-kinin and renin-angiotensin systems. It specifically examines ACE inhibitor-induced angioedema, noting its incidence, risk factors, types based on drug structure and pharmacokinetics, and mechanisms of action related to inhibition of angiotensin-converting enzyme. The diagnosis of ACE inhibitor-induced angioedema is described based on its characteristic symptoms and sites of involvement.
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Angioedema
- 1. Angioedema นพ . สุรสฤษดิ์ ขาวละออ 2/12/52
- 6. Mechanism of angioedema Clin Ped Emerg Med.2007;8:72-80 1 2 3 4 5 6 7
- 7. N Franklin. Middleton’s allergy 7 th edition 2009
- 8. N Franklin. Middleton’s allergy 7 th edition 2009
- 9. Angioedema N Franklin. Middleton’s allergy 7 th edition 2009
- 10. Angioedema N Franklin. Middleton’s allergy 7 th edition 2009
- 23. DDx of angioedema Immunol Allergy Clin N Am.2006;26:603-613 Allergy.2007;62:842-856
- 25. DDx of angioedema The America Journal of Medicine.2008;121(4):282-286
- 30. Quincke’s disease Romana’s sign & trypanosomiasis Trichinosis tsetse fly
- 36. poikiloderma ranula blepharochalasis Chelitis glandularis Fissure tongue Melkersson Rosenthal syndrome
- 38. DDx of angioedema Without wheals Normal C4 ACEI induced
- 46. 1 2 3 Nature reviews 2002
- 55. ACEI-induced angioedema Bas M et al.Allergy.2007;62:842-856
- 56. Angioedema
- 58. Angioedema
- 61. ACEI-induced angioedema Immunol Allergy Clin N Am.2006;26:725-737
- 64. The America Journal of Medicine.2008;121(4):282-286
- 65. The America Journal of Medicine.2008;121(4):282-286
- 71. ACEI-induced angioedema 64 patients Loss F/U 10 patients 54 patients, all normal lab 26 Angiotensin receptor blocker 14 Calcium channel blocker 14 others:b-blocker, diuretic,etc Arch Intern Med.2004;164:910-913
- 72. ACEI-induced angioedema Arch Intern Med.2004;164:910-913
- 77. Thank you
Editor's Notes
- Pathophysiologic mechanisms of urticaria and angioedema 1.activation occur by antigen cross-linking of IgE bound to mast cell surface IgE receptors (FceRI). Histamine causes local vasodilatation and increased vascular permeability 2.Cutaneous nerve fiber stimulation produces an axonal reflex that releases substance P potent vasodilator but also stimulates the release of additional histamine from mast cells substance P(tachykinin) another peptide substrate of ACE 3.IgE cross-linking also triggers production of mast cell membrane-associated arachidonic acid metabolites, including PG D2 through action of the COX enzyme, and leukotrienes C and D through action of the lipoxygenase enzyme 4.Complement system activation generates complement fragments C3a, C4a, and especially C5a (as anaphylatoxins), which bind to mast cell surface complement receptors and trigger histamine release 5.C3a (selective for Eo) and C5a (for N, Eo, mononuclear cell) are also chemotactic for several inflammatory cells that produce histamine-releasing factors. Histamine-releasing factors contribute to the enhancement and prolongation of the inflammatory reaction in a non–IgE-dependent manner. Increased cutaneous vascular permeability leads to extravasation of plasma proteins 6.contact of Hageman factor with cell surfaces, and subsequent activation of the kinin-forming system. Kallikrein is generated, which leads to conversion of high- molecular weight kininogen to bradykinin(potent mediator of vasodilatation and vascular permeability) 7.Cross-linking of mast cell–bound IgE by anti-IgE autoantibodies directed against Fc region of IgE molecule or by autoantibodies against mast cell surface IgE receptors (anti-FceRI) can trigger histamine release 8.Bradykinin is deactivated primarily by ACE located on pulmonary arterial endothelium mechanism of ACEinhibitor hypersensitivity reactions may involve interference with bradykinin degradation 9.Direct, nonimmunologic mechanisms include physical stimuli, such as thermal and mechanical; radiocontrast dyes (perhaps due to high osmolality); ethanol; medications such as vancomycin and opioids; and foods such as strawberries and shellfish 10.NSAID-induced reactions are thought to occur via inhibition of COX1, leading to shunting toward lipoxygenase pathway with resultant increased synthesis of cysteinyl leukotrienes 11.C1 esterase inhibitor controls spontaneous activation and downregulates both complement and kinin-forming pathways. C1 esterase inhibitor dysfunction can cause angioedema through inappropriate production of bradykinin 12.Indirectly, autoimmune IgG1 IgG3 antibodies produced in several autoimmune diseases can fix complement and generate anaphylatoxins LPO indicates lipoxygenase; HMW, high-molecular-weight.
- Fig . 19.4 Mediators released from mast cells upon IgE - mediated activation . Upon cross - linking of Fc ε RI - IgE by allergen, mast cells immediately release a host of preformed mediators from storage in secretory granules via exocytosis . Concomitantly, leukotrienes and PGD 2 are generated from arachidonic acid, and cytokine and chemokine production is induced
- Fig . 19.4 Mediators released from mast cells upon IgE - mediated activation . Upon cross - linking of Fc ε RI - IgE by allergen, mast cells immediately release a host of preformed mediators from storage in secretory granules via exocytosis . Concomitantly, leukotrienes and PGD 2 are generated from arachidonic acid, and cytokine and chemokine production is induced
- Diagram of Hageman factor ( HF )- dependent pathways of coagulation, fibrinolysis and kinin generation Reaction 1 depicts HF autoactivation Reaction 2 describes reciprocal activation of HF and prekallikrein in which high - molecular - weight ( HMW ) kininogen functions as a cofactor HFa, activated HF .
- HAE type III = estrogen dependent ;associated with exogenous Estrogen administration such as oral contraceptive, hormone replacement therapy
- ปาราสิต มีชื่อว่า Trypanosoma gambiense หรือ Trypanosoma rhodesiense มีแมลง tsetse fly เป็นพาหะนำเชื้อ พยาธิตัวกลมลำไส้ Trichinella spiralis
- -Renin = aspartic protease สร้างจาก juxtaglomerular cell in kidney -cleaves angiotensin ซึ่งสร้างจากตับได้ decapeptide angiotensin I (inactive) -ACE (known as kinase II) เป็น enzyme ชนิด non-selective dipeptidyl carboxypeptidase ซึ่งมี substrate ทั้ง angiotensin I และ bradykinin -catalyse hydrolysis of bradykinin to inactive product & A I to active A II -Chymase(non-ACE) สามารถสร้าง A II ได้ , นอกจากนี้ non-renin enzymes(tonin, cathepsin) สามารถสร้าง A II จาก angiotensiongen ได้โดยตรง
- -Angiotensin I & II can be digested by angiotensinase(peptidase) โดยจะตัดกรดอะมิโนบริเวณ Amino terminus(aminopeptidase) or carboxyl terminus(carboxypeptidase) ได้เป็นส่วนย่อยๆ เรียก A III (2-8 peptide bind to AT1, AT2) ออกฤทธิ์คล้ายกับ A II A IV(3-8 peptide bind to AT4 receptor) stimulate release of plasminogen activator inhibitor 1 (PAI 1) ซึ่งเป็น potent antithrombolytic factor Ang (1-7 peptide bind to AT3 receptor) stimulate vasodilatation & potentiate bradykinin -signal tranduction by AT1 receptor 1.AT I receptor is member of G protein-coupled-receptor superfamily 2.part of protein close to surface(red) participate in binding to A II 3.deeper amino acid resiues(blue) binding to sartan family of ARB 4.when bind to A II stimulate phospholipase C(PLC) & open calcium channels 5.PLC cleaves phosphoinositide(PIP2) to inositol triphosphate(IP3) release endoplasmic calcium and to DAG 6. ทั้ง DAG & IP3 จะไป activate protein kinase C เพื่อไปเติมฟอสเฟตให้กับโปรตีนอื่นๆในเซลต่อไป
- -AT 3 receptor ในปัจจุบัน define as Mas R ซึ่ง Ang(1-7) จะใช้ receptor ตัวนี้ในการออกฤทธิ์ Counter-regulatory กับ AT1 R -AT 2R ออกฤทธิ์ตรงข้ามกับ AT1R -AT4R purified from bovine adrenal membranes & identified as enzyme, insulin-regulated aminopeptidase(IRAP) พบใน หัวใจ , ปอด , ไต , สมอง (enhance cognitive function,Modulation of blood flow, increase natriuresis, inhibit cardiomyocyte hypertrophy)
- BKR-1 generated in pathophysiologic conditions such as inflammation, trauma, burns, shock, and allergy. The B 1 receptor is one of two of G protein-coupled receptors that have been found which bind bradykinin and mediate responses to these pathophysiologic conditions -B 1 protein is synthesized de novo following tissue injury and receptor binding leads to an increase in the cytosolic calcium ion concentration, ultimately resulting in chronic and acute inflammatory responses B 2 receptor is a G protein-coupled receptor , coupled to G q and G i . G q stimulates phospholipase C to increase intracellular free calcium and G i inhibits adenylate cyclase it is ubiquitously and constitutively expressed in healthy tissues.
- -bradykinin most potent vasodilators because capable to liberate 3 important endothelium-derived vasodilatory mediators -NO -PGI 2 - Endothelium-derived hyperpolizing factor(EDHF;34) -activation BKR-2 on endothelium lead to activation of phospholipase C via tyrosine phosphorylation Increase formation of inositol 1,4,5-triphosphate(IP3) & diacylglycerol increase intracellular calcium By liberalization from internal stores or increase calcium influx -calcium activates Ca 2+ -sensitive endothelial nitric oxide synthase(eNOS) นอกจากนั้นยังกระตุ้น Ca 2+ -sensitive phospholipase A2 ซึ่งจะไป hydrolyses membrane phospholipids ได้เป็น arachidonic acid ซึ่งจะถูกเปลี่ยนเป็น PGI 2 ตามลำดับ - ส่วน EDHF บางตำราว่าอาจได้จากการเปลี่ยน archidonic acid โดย enzyme epoxygenase -Ju & colleagues demonstrate that bradykinin activate tyrosine kinase 2(Tyk2) of janus-activated kinase(JAK)
- JAK - STAT signaling pathway takes part in the regulation of cellular responses to cytokines and growth factors . Employing Janus kinases (JAKs)or and Signal Transducers and Activators of Transcription (STATs), the pathway transduces the signal carried by these extracellular polypeptides to the cell nucleus , where activated STAT proteins modify gene expression . Although STATs were originally discovered as targets of Janus kinases , it has now become apparent that certain stimuli can activate them independently of JAKs. The pathway plays a central role in principal cell fate decisions, regulating the processes of cell proliferation , differentiation and apoptosis . It is particularly important in hematopoiesis - production of blood cells .
- -Nielsen ได้สรุปว่าในภาวะ ACEI-induce AE เกิด imbalance between production & breakdown of bradykinin -C1 inhibitor favorably suppress local over-production of bradykinin
- ในปี 2004 Cicardi & colleagues ได้ทำการ วิจัยแบบ descriptive โดยรวบรวมผู้ป่วยที่มีประวัติ AE ทั้งมี urticaria และไม่มี urticaria จำนวน 1168 คน
- -median length of ACEI before appearance AE = 12 Mo -median duration of ACEI use after appearance of 1 st episode = 12 Mo -median length of F/U = 11 Mo
- -8 คนที่ไม่ได้ผล ( no effect) แบ่งเป็น 6 คน เกิดจากสาเหตุอื่นๆ เช่น 1 คน พบว่ามี dental granuloma 1 คน เกิดจากการกินอาหารที่มี histamine ปนเปื้อน 4 คน unknown cause แม้หยุดยาแล้วยังเกิด AE 2 คนสุดท้าย เกิด AE ขณะ switch จาก ACEI เป็น ARB 1 คน switch to candesartan 2 Mo ยังพบ AE หายไปเมื่อเปลี่ยนยาเป็น β -blocker 1 คน หลังเริ่ม losatan พบ 2 nd AE episode จึงเปลี่ยนเป็น nifedipine หลัง F/U 8 Mo ไม่พบอาการอีกเลย