Angioedema 11/12/2010 BY: MOHAMMED ALSAIDAN

Angioedema Abrupt and short-lived swelling of the skin, mucous membranes, or both including the upper respiratory and intestinal epithelial linings The swelling is nonpitting, erythematous or skin-colored Areas where the skin is lax Pain is variable, but rarely itching. There is no desquamation or staining of the skin although scratching or rubbing may cause bruising.

Pathophysiology Increase in permeability of the submucosal or subcutaneous capillaries and postcapillary venules, causing local plasma extravasation and consequent swelling. A variety of vasoactive molecular mediators, by mast cells: Preformed ? synthesized ? There is a paucity of cellular infiltration in angioedema.

Epidemiology 49% of all patients with urticaria also had angioedema Angioedema occurred in 93 of 107 (87%) patients with chronic urticaria Women are more frequently affected than men Most commonly affects those 40 to 50 years old

Acute allergic angioedema Almost always accompanied by urticaria, within 1 to 2 hours of exposure to the offending allergen. It is commoner in patients who are atopic or allergic to foods or medications Pathophysiology = urticaria (the g-chains of FceR1  tyrosine kinase activation  protein kinase C activation  increase in intracellular calcium  mast cell degranulation )

Acute allergic angioedema

Clinical features: swelling can occur anywhere Risk of anaphylaxis Skin prick test vs. RAST

TREATMET ABC EPI PEN Adult Mild angioedema without signs of circulatory compromise  mg of 1:1000 SC Moderate-to-severe angioedema with signs of shock:  Adult dose is mg of 1:10,000 IV  Pediatric mg (depending on the patient's weight) of 1:1000 solution SC Diphenhydramine (50 mg) I.V. or I.M Hydrocortisone (200 mg) I.V 24 h. Observation

NSAID-induced angioedema Clinical picture resemble allergic urticaria or angioedema and are often termed ‘‘pseudoallergic” Only COX 1 inhibitors cause pseudoallergic angioedema Skin prick testing has no value urticaria/angioedema to NSAIDS vs. NSAID-induced asthma Rx: Emergency measures are as for acute allergic angioedema +/- leukotriene antagonists?

Angioedema of ACE inh. Not associated with urticaria Usually involve face + orophaynx Incidence = 0.1% to 0.2% and is 5 x more common in African Americans than white patients The most common cause of acute angioedema Rx: as for allergic but with risk of relapses after recovery

Angioedema of ACE inh. Angiotensin II receptor antagonists are tolerated by patients who have reacted to ACE inhibitors Screen for HAE

Physical urticarias

Idiopathic acquired angioedema Chronic and relapsing, and usually associated with urticaria In 30% to 50% : urticaria and the angioedematous lesions are a result of an autoimmune process Angioedema and urticaria occurred together in 49% to 87% and angioedema alone in 9 to 11% Pathophysiology = idiopathic urticaria ASST might be helpful, basopenia

Idiopathic acquired angioedema Avoid provoking factors : Aspirin Overtiredness Overexcitement overvigorous exercise alcohol overconsumption Antihistamines vs. steroids vs. others?

Gleich syndrome Episodic angioedema, urticaria, fever, weight gain, peripheral blood and skin eosinophilia Patients responded well to systemic steroids Probably closely related to the hypereosinophilic syndrome

Hereditary angioedema (HAE) Dominantly inherited defect in chromosome 11 (11q12- q13.1) Affects about 1:50,000 person (type 1) (The classic type) is a quantitative defect in (C1 INH) (type 2) is functional defect in (C1 INH) (type 3) in women with quantitatively and functionally normal C1 INH activity with a relationship to estrogenic activity

To be clinically expressed, the C1 INH plasma level should be quantitatively or functionally less than 40% of normal

Hereditary angioedema (HAE) Increase in activation of C1, leading to consumption of C2 and C4, high level of bradykinin Patients are usually asymptomatic up to puberty precipating factors minor injury such as dental maneuvers (>50%) vigorous exercise alcohol consumption emotional stress hormonal factors

Hereditary angioedema (HAE) There could be transitory prodromal nonpruritic urticarial eruption in some patients, persist for 3 to 4 days Coadministration of ACE inhibitors and estrogens is contraindicated in HAE. Associated diseases: Glomerulonephritis Sjogren’s syndrome thyroiditis, Lupus coagulopathies

Treatment ABCs (usually not life threatening) Antihistamines and corticosteroids are ineffective S.C. adrenaline (0.3 mg every 10 minutes) usually not effective but maybe helpful The mainstay treatment is: I.V. FFP or C1 inhibitor concentrate 550 plasma U in a 10-mL vial to be administered at a dose of 25 plasma U/kg body weight to a total of 1000 plasma U repeated once if necessary, It is usually effective within 3 to 4 hours, and often within minutes.

Treatment There have been reports of improvement of acute symptoms with icatibant, a specific B2 kinin antagonist Anabolic steroids increase the circulating levels of normal functional C1 INH in both type 1 and type 2 HAE risk of hepatotoxicity and liver adenomas stanazolol 2-4 mg/d danazol mg/d women : hirsutism, acne, menstrual cycle irrigularity, deep voice

Prophylaxis C1 inh concentrate before surgery, especially when intubation or tooth extraction is necessary For minor surgical procedures, tranexamic acid (1 g four times daily in adults or 500 mg four times daily in children) for 48 hours before and after the procedure increase in established maintenance doses of tranexamic acid or anabolic steroids

Acquired C1 inh. deficiency Type 1: immune complex mediated C1 and C1 inh consumption associated diseases : B-cell lymphoma (the most common) Other haematologic malignancies Type 2 : autoantibodies against C1 inh.

Treatment Treatment of the underlying disease Plasma or C1 inhibitor concentrate used for emergency For chronic disease: Plasmapheresis Cytotoxic agent Androgenic compounds e-aminocaproic acid Tranexamic acid for type II

Thank You