Kamilah Fernandez TSMU 5th Year Group#1

ANGIOEDEMA

WHAT IS ANGIOEDEMA ?
Angioedema is the pronounced swelling of the deep dermis, subcutaneous or submucosal tissue, or mucous membranes as a result of vascular leakage. Other terms, such as giant urticaria,Quincke edema,and angioneurotic edema. Angioedema is usually nonpitting and nonpruritic. Involved skin often shows no change in color or may be slightly erythematous. Angioedema is most commonly observed affecting the lips and eyes (periorbital). Other commonly involved areas may include the face, hands, feet, and genitalia. It can also affect the GI tract. Swelling that involves the larynx, tongue and upper airways are potentially life threatening owing to airway compromise and are to be treated as a medical emergency.

ANGIOEDEMA EPIDEMIOLOGY
Angioedema can affect people of all ages. Persons who are predisposed to angioedema have an increase in frequency of attacks after adolescence, with the peak incidence in the third decade of life. The World Allergy Organization (WAO) notes that urticaria and angioedema affects up to 20% of the population. In HAE, affected women tend to have more frequent attacks and run more severe clinical courses. Chronic idiopathic angioedema is more common in females than in males. Other types of angioedema do not show a strong sex preponderance. No specific racial predilection exists for angioedema. However, black individuals are more susceptible to angioedema induced by ACE inhibitors.

ANGIOEDEMA TYPES
1. Acute allergic angioedema - almost always occurs with urticaria within 1-2 hours of exposure to the allergen. Food allergies, drugs, radiocontrast media, insect venoms, natural rubber latex etc. 2. Non-allergic drug reaction -onset may be days to months after first taking the medication e.g. ACE inhibitors. Cascade of effects via kinin production, arachidonic acid metabolism and nitric oxide generation. 3. Idiopathic angioedema -(frequently chronic and relapsing and usually occurs with urticaria) cause unknown but may be associated with autoimmune disorders.

ANGIOEDEMA TYPES
4. Hereditary angioedema - Inherited AD abnormal gene that causes a deficiency of a normal blood protein. 3 types: Type 1 and II mutation of C1NH (SERPING1) gene on chromosome 11, encoding C1 inhibitor protein. Type III mutation in F12 gene on chromosome 12, encoding coagulation factor XII. Type 1 results in low levels and function of circulating C1 inhibitor; Type II has normal levels of C1 inhibitor protein but reduction in function Decreased C1 inhibitor activity leads to excessive kallikrein, which in turn produces bradykinin, a potent vasodilator 5. Acquired C1 inhibitor deficiency-Acquired during life rather than inherited, may be due to B-cell lymphoma or antibodies against C1 inhibitor.

ANGIOEDEMA ETIOLOGY
More than 38% of chronic angioedema is idiopathic. Trauma, surgical procedures, and stress are common nonspecific triggers for angioedema attacks. Angioedemas with identifiable etiologies include those caused by the following: Hypersensitivity (e.g.food, drugs, or insect stings) Physical stimuli (e.g. cold or vibrations) Autoimmune disease or infection ACE inhibitors NSAIDs C1-INH deficiency (hereditary and acquired)

ANGIOEDEMA ETIOLOGY

ANGIOEDEMA PATHOPHYSIOLOGY
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 mediator. Hereditary angioedema (HAE), angiotensin-converting enzyme (ACE) inhibitorinduced angioedema, and certain idiopathic angioedemas are examples of bradykinin-mediated angioedema; bradykinin levels are directly elevated in the blood.

ANGIOEDEMA PATHOPHYSIOLOGY

ANGIOEDEMA PATHOPHYSIOLOGY

ANGIOEDEMA CLINICAL PRESENTATION

Swelling of the face (eg, eyelids or lips), tongue, hands, and feet Local burning sensation and pain without pronounced itchiness or local erythema Abdominal pain (sometimes the only presenting symptom of angioedema) Throat tightness, voice changes, and breathing trouble (indicators of possible airway involvement)

ANGIOEDEMA CLINICAL PRESENTATION

ANGIOEDEMA CLINICAL PRESENTATION

ANGIOEDEMA CLINICAL PRESENTATION

ANGIOEDEMA CLINICAL PRESENTATION

ANGIOEDEMA CLINICAL PRESENTATION

ANGIOEDEMA DIAGNOSIS
Majority of cases it is based on history and physical examination. Examination in patients with suspected angioedema includes the following: Dermatologic Areas of swelling with or without erythematous skin, often with ill-defined margins; the face, extremities, and genitalia are most commonly affected GI No specific findings or there may be abdominal distention and signs consistent with bowel obstruction; changes in bowel sounds and tenderness may be present; the clinical picture may resemble that of an acute abdomen Upper airway Direct visualization of the uvula or tongue swelling; laryngoscopy is needed to assess laryngeal or vocal cord involvement.

ANGIOEDEMA DIAGNOSIS
Laboratory Test Most mild cases of angioedema do not require laboratory testing. Suspected allergies to food, stinging insects, latex, and antibiotics can be screened and diagnosed. For angioedema without urticaria (especially those with recurrent episodes), diagnostic tests should include the following: C4 level C1 esterase inhibitor (C1-INH) quantitative and functional measurements C1q level Sometimes CBC, ESR, CRP, D-dimer level ,urinalysis Thyroid studies, particularly in women or in patients with a family history of thyroid disease or other autoimmune diseases

ANGIOEDEMA DIAGNOSIS

ANGIOEDEMA DIAGNOSIS

ANGIOEDEMA DIAGNOSIS
IMAGING STUDIES It is not needed in most patients but it is used when internal organ involvement is suspected Plain abdominal films These may show a stacked coin or thumbprint appearance of the intestines Abdominal ultrasonography This may show ascites. Abdominal computed tomography This may show severe edema of the bowel wall Chest radiography This may show pleural effusion Soft-tissue neck radiography This may show soft-tissue swelling.

ANGIOEDEMA TREATMENT
The primary goal of medical treatment for angioedema is to reduce and prevent swelling and the discomfort and complication. Epinephrine and supportive care should be used when laryngeal angioedema is suspected regardless of the etiology. In histamine-mediated angioedema, second-generation antihistamines are often used as first-line treatment. Firstgeneration antihistamines can be used as add-on therapy when a second-generation agent cannot provide adequate symptom relief. Corticosteroids can be used in severe cases of histaminemediated disease. In bradykinin-mediated angioedema, antihistamines do not work, and corticosteroids have limited or no value. Instead, fresh frozen plasma, antifibrinolytics, C1-INH, ecallantide, and icatibant are used to manage the angioedema

ANGIOEDEMA TREATMENT
MEDICATIONS USED IN ANGIOEDEMA MANAGEMENT; Alpha- and beta-adrenergic agonist agents (eg, epinephrine) 1st generation antihistamines (eg, diphenhydramine, chlorpheniramine, cyproheptadine, hydroxyzine hydrochloride) 2nd generation antihistamines (eg, cetirizine, desloratadine, fexofenadine, levocetirizine, loratadine) Histamine H2 antagonists (eg, ranitidine, cimetidine) Leukotriene receptor antagonists (eg, montelukast, zafirlukast) Tricyclic antidepressants (eg, doxepin) Corticosteroids (eg, prednisone, methylprednisolone, prednisolone) Androgens (eg, danazol, oxandrolone) Antifibrinolytic agents (eg, aminocaproic acid, tranexamic acid) Immunomodulators (eg, human C1-INH, ecallantide, icatibant)

ANGIOEDEMA PROGNOSIS
The prognosis for patients with angioedema depends on the etiology and varies as follows: Angioedema with identifiable causes If the trigger(s) can be identified and avoided, angioedema can be prevented Angioedema without identifiable causes There is a tremendously variable clinical course, ranging from mild to severe and a few days to many years; the response to conventional treatment is less unpredictable HAE Lifelong treatment is often required AAE Outcome depends on the treatment of underlying lymphoproliferative or autoimmune disorders