Urticaria دکتر افشین شیرکانی فوق تخصص آسم و آلرژی و بیماری های نقص ایمنی عضو آکادمی آسم و آلرژی و ایمونولوژی آمریکا استادیار دانشگاه

Urticaria is a type of skin rash, which is raised, pruritic, erythematous, and transient ( lasts less than 24 hours at the same location), and is also known as hives It is the same wheal-and-flare-type skin reaction as observed in the positive skin prick test

Acute:< 6 Wks : It occurs in up to 20% of the population and is often associated with drug, food, or other allergy, or with infection Chronic : > 6Wks : It occurs in about 0.5% of the population; in about 45% of CIU patients is an autoimmune disease, due either to IgG antibody to the α subunit of the high-affinity IgE receptor or, less commonly, to anti-IgE antibody

Pathology 50% : Urticaria + Angioedema 40% : Only Urticaria dilated blood vessels and edema in the superficial dermis Angioedema in that the latter occurs in the deep dermis and subcutaneous tissue 50% : Urticaria + Angioedema 40% : Only Urticaria 10% : Only Angioedema

Mediators Multiple vasoactive mediators are released after the binding of antigen to IgE on basophiles or tissue mast cells Mast cell: histamine, prostaglandin D, leukotrienes LTC4 and LTD4, and PAF Complement system: anaphylatoxins C3a, C4a, and C5a; also histamine Hageman factor-dependent pathway: bradykinin Mononuclear cells: histamine-releasing factors and chemokines

Etiologies Infections: bacterial (Helicobacter pylori) Transfusion reactions Chronic idiopathic urticaria Hereditary urticaria, such as familial cold urticaria and amyloidosis, with deafness and urticaria (eg. Muckle-Wells syndrome) Inhalation or contact with allergens NSAIDs and/or drug reactions and neoplasms such as Schnitzler’s syndrome Gut: foods or food additives Mastocytosis (systemic): Urticaria pigmentosa Autoimmune urticaria Physical urticarias: different types Systemic lupus erythematosus, carcinoma, and other collagen vascular diseases

Physical Urticaria Cold Urticaria Urticaria occurs on cold-exposed areas of the body Systemic reactions can occur with shock (patient should avoid swimming in lakes) Drug of choice classically is cyproheptadine (C for cold); other antihistamines also work Idiopathic cold urticaria (most common), induced by histamine after cold exposure; could be antibody-mediated and passively transferred; IgE, IgG, and IgM.

Cholinergic Urticaria and Local Heat Urticaria Pruritic, small macules, and papules occur in response to heat, exercise, or emotional stress Occurs primarily in teenagers and young adults Autologous sweat sensitivity: sweat may cause basophil degranulation in sensitive subjects who have positive skin test to own sweat Drug of choice: Hydroxyzine (H for heat).

Dermatographism Very common; affects 2%-5% of population. Stroking of the skin results in linear wheals, which may persist as long as 30 minutes. Passive transfer studies suggest an IgE- mediated reaction.

Solar Urticaria Rare, brief exposure to light causes urticaria within one to three minutes; most affected patients are in third and fourth decade of life. Type I and IV may be passively transferred (possibly due to IgE).

Aquagenic Urticaria Small wheals result from contact with water, independent of temperature.

Chronic Idiopathic Urticaria (CIU) exclusion after ruling out acute urticaria and physical urticarias; identifiable etiologies may be found in less than 2% of cases(20% physical and 80% Idiopathic) . 30%-40% CIU autoimmune cause, IgG or IgM antibodies against high affinity IgE receptor α-chain, rarely anti-IgE antibodies Detected through autologous serum skin test and basophil histamine release assays. Thyroid autoantibodies presents in more than 20% of patients with CIU, where antithyroid peroxidase is greater than antithyroglobulin antibody.

Laboratory Tests Blood Tests Blood tests are not helpful for acute urticaria. For chronic urticaria without identified etiology, limited blood tests may be obtained, including CBC Diff, ESR, and antithyroglobulin,U/A,LFT,S/E,CXR,ANA

Specific Testing Procedures for Physical Urticaria : Cold urticaria: ice cube test Vibratory urticaria: vibration with laboratory vortex for four minutes Aquagenic urticaria: challenge with tap water at various temperatures Heat urticaria: test tube water at 44C (111F) Cholinergic urticaria: exercise for 15-20 minutes or leg immersion in 44C (111F) bath Pressure urticaria: Sandbag test Dermographism: Stroking with narrow object (eg, tongue blade and fingernail).

Treatment Elimination of trigger factors H1-antihistamines, preferably nonsedating And H2-receptor antagonists chronic urticaria, low-dose daily or alternate-day corticosteroids or other immunomodulators may be needed, such as leukotriene antagonists, cyclosporine, and tacrolimus.

Urticarial Vasculitis and Hypocomplementemic Urticarial Vasculitis Syndrome Urticarial Vasculitis (UV) : Skin lesions generally last longer than urticaria and they tend to be less pruritic. Often described as painful and burning. Histopathology shows leukocytoclasis and vessel wall damage. Lesions can resolve with purpura or hyperpigmentation remaining. Hypocomplementemic Urticarial Vasculitis Syndrome (HUVS) : Urticaria with hypocomplementemia. Also associated with angioedema, obstructive lung disease, uveitis, and episcleritis. Laboratory findings include ↓C3 or C4, ↓↓C1q, anti-C1q antibodies, and ↑ESR.

Angioedema 1. Histamine dependent : 90%: EPI-Antihistamine- corticosteroid response 2. Kallikrein-Kinin : 10%: NO response to above Autoactivation of factor XII Decrease of C4,C1INH,C1q Loss of function of C1INH ACE (major enzyme for bradykinin degradation)

HAE patients have normal laboratory (Type III ), Female Hereditary angioedema (HAE) AD Deficiency of Cl inhibitor: 85% ( type I) :decrease C1INH, C4,C2(Attack) Dysfunctional Cl-esterase inhibitor:15% (type II) :Nl C1INH, decrease C4,C2(Attack) HAE patients have normal laboratory (Type III ), Female 25% of cases occur in patients without any family history

Clinical manifestation of HAE unpredictable, recurrent attacks of episodic swelling that involves: Face Peripheral extremities Genitalia Abdomen Oropharynx and pharynx

Triggers of HAE Trauma Menses Stress Fever Exercise Surgery Stinging

Kalbitor (for acute attacks in children ≥16 years of age) Treatment of HAE HAE attacks: Berinert (for acute facial or abdominal attacks in children ≥13 years old) Kalbitor (for acute attacks in children ≥16 years of age) Cinryze (for prophylaxis in adolescents and adults) FFP HAE prophylaxis: Androgen (Danasol) , Tranexamic acid,FFP