Acute Urticaria

There is no identifiable trigger in more than 50% of cases of acute urticaria. Viral infections are the most common cause in children. Hives typically occur a few days after the start of viral symptoms. In regards to other potential triggers, urticaria should be classified as allergic or nonallergic. Allergic, or IgE-mediated, urticaria can be attributed to food, drug, or insect allergies. Unlike in adults, in whom less than 1% of acute urticaria is thought to be caused by food allergy, food allergy needs to be considered in children because it is a more common cause of acute urticaria. Nonallergic, or non–IgE-mediated, urticaria may be attributed to an immune response, such as in serum sickness, or to pseudoallergens, such as aspirin and other salicylates. Vasoactive amines found in cheeses, beer, and wine can also elicit urticaria. In general, IgE-mediated food allergies, specifically to milk, wheat, egg, soy, and nuts, are more common than non–IgE-mediated food-induced hives.

Chronic Idiopathic Urticaria

CIU, as the name implies, typically lacks an identifiable, consistent trigger. The episodic onset of disease is more commonly observed in adults than children. The disease duration is on average 3 to 5 years, with greater duration if severe disease, angioedema, or autoimmune features are present. The pathogenesis of CIU is still unknown, although autoantibodies and cells typically involved in IgE-mediated reactions, such as mast cells and basophils, have been implicated. About 30% to 40% of patients with CIU are classified as having autoimmune urticaria, a subgroup of CIU defined by the presence of histamine-releasing autoantibodies. The majority of these autoantibodies are directed against the α subunit of the high-affinity receptor, FcεRI; the remainder target IgE. These autoantibodies have been hypothesized to be pathogenic, although this remains controversial because they can also be found in healthy individuals, in addition to those with other autoimmune diseases, such as systemic lupus and dermatomyositis. Injection of autologous serum, also known as the autologous serum skin test (ASST), leads to a wheal-and-flare response in CIU patients, suggesting that the causative agent is in the serum. Patients with CIU have a higher prevalence of other autoantibodies such as antimicrosomal and antithyroglobulin thyroid autoantibodies and a higher frequency of certain HLA class II alleles (DR4, DQ8) associated with autoimmunity.

More recently, the role of mast cells and basophils has been investigated. Skin biopsies of patients with CIU demonstrate mast cell degranulation accompanied by increased mast cell releasibility that reverses with disease remission. Basophils, which typically are not present in the skin, are observed in both lesional and nonlesional CIU skin biopsies. Basopenia has been described in CIU and is a marker of more severe disease. More recently, basophil activation markers have been shown to be enhanced in CIU patients along with defects in basophil signaling through the IgE receptor.

Physical Urticaria

Physical urticarias have a specific trigger that directly induces hives within minutes, with hives lasting minutes to a few hours. Physical urticarias are further classified into multiple subtypes (Table 20-1), each having a different physical trigger; thus, an individual can have more than one subtype. Mast cell degranulation is included in the pathogenesis of most subtypes of physical urticaria, including dermatographic, cholinergic, cold, and solar urticaria, but serum immunoglobulin may also be involved as demonstrated by passive transfer experiments.