**4. Etiology and pathogenesis**

Drugs, foods, viral and parasitic infections, insect stings and contact allergens are present among the most common causes of acute urticaria [8]. Drugs most commonly implicated in acute urticaria are antibiotics (penicillins and sulfonamides), nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, opiates and narcotics. Foods, such as milk, eggs, nuts, fish and shellfish are common offenders, as well as food additives, such as tartrazine dyes, benzoic acid derivatives like sodium benzoate. Approximately 50% of cases of acute urticaria are idiopathic [5, 9].

The relationship between stress and chronic spontaneous urticaria is not fully understood. There are reports showing stressful life events, such as loss of close family member, financial problems, major personal illness preceded onset or exacerbation of the disease in a considerable subset of patients with chronic spontaneous urticaria [10, 11]. Although many patients report stress to exacerbate their disease, there is a lack of well-controlled studies on this subject [3].

In 35–40% of patients with chronic urticaria, circulating immunoglobulin G (IgG) autoantibodies against alpha subunit of the IgE receptors are found and in 5–10% of chronic urticaria patients, there is IgG antibody to IgE. This subtype of chronic urticaria is designated as chronic autoimmune urticaria [12]. The remainder of the patients with chronic urticaria is classified under the name of chronic idiopathic urticaria. In this form of urticaria, the mechanism for stimulation of mast cells is unknown [5].

Pathophysiological mechanisms leading to formation of urticaria and angioedema can be immune-mediated, complement-mediated, non-immune–mediated and autoimmune-mediated [13]. As in most cases of acute urticaria, immune-mediated urticaria is an IgE-mediated hypersensitivity reaction. This allergic reaction is commonly triggered in response to drugs, foods and insect bites [7, 13]. Complement activation leading to release of C3a, C4a and C5a can stimulate mast cells. Non-immune–mediated urticaria involves direct activation of mast cells by non-IgE mechanisms examples of which are physical stimuli, radiocontrast dyes, drugs, such as opiates and vancomycin. Autoimmune urticaria involves autoantibodies causing mast cell degranulation [12, 13]. As noted all mechanisms lead to activation of mast cells causing liberation of histamine, leukotriene C4 and prostaglandin D2. These vasoactive mediators cause vasodilatation and extravasation of plasma from postcapillary venules. In 4–5 hours, an inflammatory cytokine response including tumor necrosis factor, interleukin 4 and interleukin 5 recruits a perivascular inflammatory infiltrate. The result is the formation a pruritic urticarial plaque or angioedema [7].
