Urticaria is a vascular reaction of the skin marked by the transient appearance of smooth, slightly elevated patches (wheals) that are erythematous and are often attended by severe pruritus. The eruption rarely lasts longer than 2 days but may be recurrent. Chronic urticaria is defined as urticaria with recurrent episodes lasting longer than 6 weeks.





Acute urticaria is more common and affects 4.5-15% of children in the United Kingdom, whereas chronic urticaria is thought to affect 0.1-3% of children in the United Kingdom. Acute urticaria differs from chronic urticaria in that a cause is more frequently established (eg, acute infection, allergen ingestion). In either case, the presence of urticaria may significantly impair quality of life. Children commonly miss significant periods of school because of a lay perception that the condition is infectious or allergic and a fear that the child is unwell. Approximately 50-80% of children with chronic urticaria also have accompanying angioedema. (See Angioedema.)

Although urticaria results from transient extravasation of plasma into the dermis, angioedema is the subcutaneous extension of urticaria that results in deep swelling within subcutaneous sites. Papular urticaria in children is characterized by 10-mm to 20-mm wheals surrounding 2-mm to 4-mm red papules. Physical urticaria typically involves 10-mm to 20-mm red blotchy macules with a 0.1-mm wheal in the center.

The development of urticaria can be an isolated event without systemic reaction or it can be a prelude to the development of an anaphylactic reaction.






Pathophysiology
Histamine is the primary chemical mediator of transient urticaria. The mast cell is central in all forms of transient urticaria. Histamine may be directly released from cutaneous mast cells in response to certain allergens or medications. Specific immunoglobin E (IgE) antibodies bind to mast cell surfaces that recognize certain antigens (eg, penicillin, certain foods, insect venom), causing the release of histamine after binding with antigen. In infection, complement fragments (eg, C3a) may activate mast cells to release histamine. Eicosanoids may also induce mast cell mediator release, and other cytokines have been implicated in urticaria. Papular urticaria represents a delayed hypersensitivity reaction in which basophil infiltrates can be found around dermal blood vessels. In physical urticaria, neuropeptide and complement products, in addition to histamine, are suspected to cause skin lesions.

In children, physical factors such as pressure or cold exposure are the most commonly diagnosed precipitating factors for chronic urticaria; other factors account for less than 1% of cases. Interestingly, one study reported that 30% or more of children with chronic urticaria have an autoimmune etiology with positive autologous serum skin test (ASST) findings. Also, approximately 4% of children with chronic urticaria have positive antithyroid antibodies, although most patients with positive antithyroid antibodies remain euthyroid.






A diagnostic skin biopsy should be considered, especially in patients who present with features such as fever, painful lesions, arthralgia, elevated erythroid segmentation rate, or lesions that last 24 hours or longer or lesions that resolve with residual petechiae or purpura. Biopsy findings may reveal a leukoclastic angiitis rather than the non-necrotizing vasculopathy that is typical in chronic urticaria. Henoch-Schönlein purpura is the most common cause of acute urticarial vasculitis in children. The pathology may show immunoglobulin A (IgA) deposits in the vessels.


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An association between childhood chronic urticaria and thyroid autoimmunity has been postulated. Whether the association is causal is unclear because most children present with hyperthyroid symptoms or hypothyroid symptoms before or after the onset of chronic urticaria and because the urticarial symptoms do not always improve with thyroxin-replacement therapy. Nonetheless, ongoing thyroid function monitoring is encouraged in children with chronic urticaria and thyroid autoimmunity.

An association has been reported between chronic urticaria and celiac disease, which may improve if a gluten-free diet is followed.

An association of Helicobacter pylori and chronic idiopathic urticaria has been reported in India.1 All patients underwent endoscopy with antral biopsy for urease and histopathology to identify H pylori–associated gastritis. Infected patients were given H pylori eradication therapy. Eradication of bacterium was confirmed by fecal antigen assay. The response of H pylori eradication therapy in patients with chronic idiopathic urticaria was determined to be significant. H pylori should be included in diagnostic workup for patients with chronic idiopathic urticaria.

The immunologic characterization of chronic idiopathic urticaria, regarding the cytokine profile, has been reported.2 The study examined levels of circulating inflammatory cytokines, cytokine production in response to phytohemagglutinin, a T-cell mitogen, and cytokine mRNA expression by peripheral blood mononuclear cells in patients with chronic idiopathic urticaria. Authors concluded that immunologic dysregulation occurs in chronic idiopathic urticaria, revealing a systemic inflammatory profile associated with disturbed cytokine production by T cells, mainly related to increase of interleukin (IL)-17 and IL-10 production.

A study reported investigation of relationship between human leukocyte antigen (HLA) class I and class II antigens and immune pathogenesis of chronic urticaria in Turkey.3 The study revealed the association of HLA-B44, HLA-DRB1*01 and HLA-CRB*15 alleles with idiopathic chronic urticaria, indicating a genetic component should be considered in the pathogenesis.

Frequency
United States






Urticaria is common in infancy and childhood, although the exact frequency is unknown. Urticaria affects 15-25% of the US population

Several large studies indicate that 3% of preschool-aged children and 2% of older children are affected.
Chronic idiopathic urticaria, in which lesions of an unknown etiology last longer than 6 weeks, is estimated to occur in as much as 3% of the population.

Mortality/Morbidity

Patients may experience recurrence of rash.
Urticaria can be an isolated event. Without recurrence, the prognosis is good.
Urticaria may be a clinical feature of anaphylaxis. In that case, the mortality rate is significant.

Race

Urticaria has no known racial predilection.

Sex

In children, both sexes are affected with equal frequency.
Chronic urticaria tends to occur in females, especially adults.


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Age

Several large studies indicate that 3% of preschool-aged children and 2% of older children are affected.
Acute urticaria usually occurs in children, whereas chronic idiopathic urticaria is more common in adults.





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