Contact Urticaria
Contact urticaria develops at the site(s) of contact of an urticant and can be divided into an allergic subgroup caused by an IgE-allergen interaction and a nonallergic subgroup that is IgE independent. The allergic form typically is seen in children with atopic dermatitis sensitized to environmental allergens such as grass, animals, food, or latex, and it may be complicated by anaphylaxis. Natural rubber latex is one of the most important causes today.27 This type appears within minutes, fades within 2 hours, and is partially inhibited by antihistamines. Nonallergic contact urticaria is caused by the direct effect of the urticant on blood vessels and includes irritants such as benzoic acid and cinnamic aldehyde in cosmetics. It may take 45 minutes for lesions to appear and urticaria is partially inhibited by NSAIDs.
Angioedema Without Wheals
It is useful to classify angioedema occurring without wheals as a separate entity because its etiology may be associated with hereditary angioedema, which must be excluded. The condition usually is idiopathic or caused by a drug reaction to angiotensin-converting enzyme inhibitors, aspirin, or NSAIDs. Hereditary angioedema is a rare autosomal-dominant condition with a prevalence between 1:10,000 and 1:150,000 in the general population and is caused by a deficiency (type 1, 85%) or dysfunction (type 2, 15%) of C1 inhibitor.28 A low level of C4 in the serum is a constant and diagnostic feature. A third type affecting primarily women and exacerbated by estrogens recently has been described.28 Patients have lifelong episodic angioedema and may experience colicky abdominal pain. Laryngeal involvement can be life threatening. Treatment is difficult and involves fluid replacement and purified C1 inhibitor concentrate for acute attacks (not approved in the United States) and prophylactic treatment with anabolic androgens and antifibrinolytics.28
Diagnosis
The diagnosis of urticaria is primarily clinical; extensive laboratory tests are very rarely needed—only when indicated by the patient history.3 Some authors argue that laboratory investigations are unnecessary for mild ordinary urticaria responding to antihistamines.29 Taking a thorough patient history has been found to be almost as effective in identifying a cause as a complete diagnostic evaluation.30 In acute urticaria, if the history indicates a type 1 hypersensitivity reaction, confirmation is possible by a prick test or laboratory radioallergosorbent tests.3 Many physical and contact urticaria can be confirmed by a challenge of the offending agent. An initial baseline investigation with a complete blood count and erythrocyte sedimentation rate should be taken in more severe cases to identify any internal disease or raise the possibility of urticarial vasculitis.17 Of note, a biopsy is more sensitive and specific for ruling out urticarial vasculitis than are a complete blood count and erythrocyte sedimentation rate.
A search for thyroid autoantibodies is appropriate for all chronic urticaria not responding to first-line therapies with antihistamines, especially when autoimmune urticaria is suspected.2 Further investigations are guided by clinical suspicion, which may include a skin biopsy, autoimmune screening, urinalysis, serum cryoglobulins, and hepatitis B and C serology.31 The only available test to screen for autoantibodies against the IgE receptor is the autologous serum skin test. This test should be performed with care because infections could be transmitted, particularly if, by mistake, patients were not injected with their own serum.31 Measurement of C4 is indicated only in patients who present with angioedema alone and should be followed by a determination of the levels and function of C1 inhibitor, if C4 is below reference range.29
Management and Treatment
Management of urticaria depends on its cause. Aggravating factors should be identified from the history, and triggering stimuli for physical urticaria should be avoided. Simple cooling lotions such as menthol 1% or 2% in an aqueous cream often are useful.32 Aspirin and NSAIDs should be avoided because they aggravate symptoms in 30% of patients.33 Patients taking low-dose aspirin for its antithrombotic properties usually can continue regular treatment. Avoiding codeine and other opiates also is recommended because an enhanced skin test reaction may be found in chronic urticaria.34 Avoiding dietary pseudoallergens, such as food coloring and natural salicylates, is controversial.14,35 This generally has only a small role unless proven by a double-blinded placebo-controlled challenge.2
The mainstays for treatment of urticaria are oral antihistamines, as they reduce pruritus and wheal duration and numbers. Oral antihistamines have been reported to produce moderate or good response in 44% to 91% of patients with all types of urticaria.36,37 Antihistamines can be grouped into first-generation (sedating), second generation (minimally sedating), third-generation (nonsedating), and H2 antagonists.17 The physiologic and pathologic actions of histamine are mediated through 4 histamine receptor subtypes: H1, H2, H3, and H4.38 The erythema, wheal formation, and itching associated with urticaria are mainly due to activation of H1 receptors and the less contributory role of H2 receptors.38 Histamine H3 receptors are located presynaptically on postganglionic sympathetic norepinephric nerves, including sympathetics innervating the heart and blood vessels. The contribution of H3 receptors to skin responses mediated by histamine has not been fully elucidated. However, in a recent experimental study, the authors reported that the combination of H1 and H3 antagonists might be a novel approach for the treatment of urticaria.38