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

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 compromise0.3-0.5 mg of 1:1000 SCModerate-to-severe angioedema with signs of shock:Adult dose is 0.3-0.5 mg of 1:10,000 IV Pediatric0.15-0.3 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 50-300 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