Urticaria & Angioedema BY Omar Younis Abdullah

Urticaria common and distinctive reaction pattern. Urticaria, also referred to as hives or wheals, is a common and distinctive reaction pattern. Hives may occur at any age 20% of the population will have at least one episode. Urticaria is classified as acute or chronic. Angioedema frequently occurs with acute urticaria, which is more common in children and young adults. Chronic urticaria is more common in middle-aged women and commonly accompanies angioedema. The cause of acute urticaria is known in many cases. The cause of chronic urticaria is determined in less than 5% to 20% of cases.

The evolution of urticaria is a dynamic process, new lesions evolve as old ones resolve. Hives result from localized capillary vasodilation, followed by transudation of protein-rich fluid into the surrounding tissue; they resolve when the fluid is slowly reabsorbed. The edema in urticaria is found in the superficial dermis. Lesions of angioedema are less well demarcated and the edema is found in the deep dermis or subcutaneous/submucosal locations.

Wheal

Clinical Classification of Urticaria/Angioedema 1. Ordinary urticaria (recurrent or episodic urticaria not in the categories below) 2. Physical urticaria (defined by the triggering stimulus): Adrenergic urticaria Aquagenic urticaria Cholinergic urticaria Cold urticaria Delayed pressure urticaria Dermographism Exercise-induced anaphylaxis Localized heat urticaria Solar urticaria Vibratory angioedema 3. Contact urticaria (induced by biologic or chemical skin contact) 4. Urticarial vasculitis (defined by vasculitis as shown by skin biopsy specimen) 5. Angioedema (without wheals) Duration of hives???

Histamine is the most important mediator of urticaria. PATHOPHYSIOLOGY Histamine is the most important mediator of urticaria. Histamine is produced and stored in mast cells. A variety of immunologic, nonimmunologic, physical, and chemical stimuli cause histamine release. Histamine causes localized capillary vasodilatation, which allows vascular fluid to leak between the cells through the vessel wall, contributing to tissue edema and wheal formation. The “triple response” of Lewis??? Blood vessels contain two (and possibly more) receptors for histamine. The two most studied are H1 and H2.

ACUTE URTICARIA If the urticaria has been present for less than 6 weeks, it is considered acute. ETIOLOGY 1. IgE-MEDIATED REACTIONS  Circulating antigens such as foods, drugs, insect stings, natural rubber latex or inhalants interact with cell membrane–bound IgE to release histamine. 2. COMPLEMENT-MEDIATED, OR IMMUNE-COMPLEX-MEDIATED, ACUTE URTICARIA Administration of whole blood, plasma, immunoglobulins, and drugs or by insect stings. 3. NONIMMUNOLOGIC RELEASE OF HISTAMINE Acetylcholine, opiates, polymyxin B, and strawberries, aspirin/NSAIDs.

CHRONIC URTICARIA Patients who have a history of hives lasting for 6 weeks or more are classified as having chronic urticaria (CU). The etiology is often unclear. The morphology is similar to that of acute urticaria but lesions are slightly deeper. CU is more common in middle-aged women and is infrequent in children. Individual lesions remain for less than 24 hours but the diasease continues for weeks, months, or years Angioedema occurs in 50% of cases and rarely affects the larynx. About 70% of patients with CU have physical urticarias. Aspirin/NSAIDs, penicillin, ACEIs, opiates, alcohol, fever, and stress exacerbate UC.

CU also results from the cutaneous mast cell release of histamine. Over 30% of CU patients have autoimmune phenomena: positive autologous serum skin tests, antibodies to the alpha subunit of the basophil IgE receptor and to IgE, and thyroid autoimmunity. There is a significant association between chronic urticaria and autoimmune thyroid disease. Most patients are women. Most patients are asymptomatic and have thyroid function that is normal or only slightly abnormal.

Evaluation and management of acute & chronic urticaria History and physical examination Lab. Tests Allergen testing Rx [1st (Antihistamines), 2nd (oral steroids) and 3rd (IV Ig) line agents] Other measures

PHYSICAL URTICARIAS Physical urticarias are induced by physical and external stimuli. They typically affect young adults. More than one type of physical urticaria can occur in an individual. Provocative testing confirms the diagnosis. Most physical urticaria forms persist for about 3 to 5 years or longer. Duration of individual lesions?

Dermographism Most frequent Stroking the skin, toweling, clothing. Starts in minutes, lasting 2-3 hours. Clinically: irregular pruritic wheals. No systemic symptoms Testing (Darier’s sign) Rx

Delayed pressure urticaria Frequent Prolonged pressure (belt, bra, manual work, standing, sitting on a hard surface). Starts within 3-12 hrs. lasting 4-36 hrs. Clinically: diffuse tender swelling. Flu-like symptoms Testing? Rx (oral steroids)

Cholinergic urticaria Very frequent General overheating of body Starts in 2-20 minutes, lasting ½ - 2 hour. Clinically: tiny papular pruritic wheals. Anaphylaxis and angioedema may occur. Testing: exercising. Rx

ANGIOEDEMA Syndromes of Angioedema Angioedema AE (angioneurotic edema) is a hive-like swelling caused by increased vascular permeability in the subcutaneous tissue of the skin and mucosa and the submucosal layers of the respiratory and GI tracts. Hives and angioedema commonly occur simultaneously. Syndromes of Angioedema Idiopathic recurrent AE   Allergic (IgE-mediated) angioedema Medication-induced (e.g., ACE inhibitors)  HAE (hereditary angioedema): 1. Type I: deficiency of C1 INH protein   2. Type II: dysfunctional C1 INH protein 3. Type III: coagulation factor XII gene mutation  AAE (acquired angioedema): 1. Type I: associated with lymphoproliferative diseases 2. Type II: autoimmune (anti–C1 INH antibody)  Episodic angioedema with eosinophilia (Gleich’s syndrome)  Thyroid autoimmune disease–associated AE

Hereditary angioedema Type 1 is the most common and results from a lack of functional C1 esterase inhibitor causing plasma kallikrein activation, which leads to the production of the vasoactive peptide bradykinin. Transmitted as an autosomal dominant trait. The disease affects between 1 in 10,000 and 1 in 50,000 persons. The disease begins in late childhood or early adolescence. Many have ancestors and family members who died suddenly from asphyxia. Mortality rate can reach up to 30%. Patients live in constant dread of life-threatening laryngeal obstruction which occurs in about 65% of cases. Minor trauma, mental stress, and other unknown triggering factors lead to the release of vasoactive peptides that produce episodic swelling. Histamine has no role in this type.

Clinical presentation? Investigations C1 INH (quantity and function) low, C4 low , C1q normal , 24 hr urine histamine normal , tryptase normal. Treatment: Acute attacks (C1 INH conc., danazol, tranexamic acid, FFP) Prophylaxis (danazol, tranexamic acid)