Urticaria (Hives) and Angioedema

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Chapter 142 Urticaria (Hives) and Angioedema

Urticaria and angioedema affect 20% of individuals at some point in their lives. Episodes of hives that last for <6 wk are considered acute, whereas those that occur at least twice a week for >6 wk are designated chronic. The distinction is important, because the causes and mechanisms of urticaria formation and the therapeutic approaches are different in each instance.

Etiology and Pathogenesis

Acute urticaria and angioedema are often caused by an allergic immunoglobulin (Ig) E–mediated reaction (Table 142-1). This form of urticaria is a self-limited process that occurs when an allergen activates mast cells in the skin. Systemically absorbed allergens that can induce generalized urticaria include foods, drugs (particularly antibiotics), and stinging insect venoms. If an allergen (latex, animal dander) penetrates the skin locally, hives can develop at the site of exposure. Acute urticaria can also result from non–IgE-mediated stimulation of mast cells, caused by radiocontrast agents, viral agents including hepatitis B and Epstein-Barr virus, opiates, and nonsteroidal anti-inflammatory agents. The diagnosis of chronic urticaria is established when lesions recur at least twice a week for > 6 wk and are not physical urticaria or recurrent acute urticaria with repeated exposures to a specific agent (Table 142-2). Often, chronic urticaria is accompanied by angioedema. Rarely, angioedema occurs without urticaria.

Table 142-1 ETIOLOGY OF ACUTE URTICARIA

Foods Egg, milk, wheat, peanuts, tree nuts, soy, shellfish, fish, strawberries (direct mast cell degranulation)
Medications Suspect all medications, even over-the-counter or homeopathic
Insect stings Hymenoptera (honeybee, yellow jacket, hornets, wasp, fire ants), biting insects (papular urticaria)
Infections Bacterial (streptococcal pharyngitis, Mycoplasma, sinusitis); viral (hepatitis, mononucleosis [Epstein-Barr virus], coxsackievirus A and B); parasitic (Ascaris, Ancylostoma, Echinococcus, Fasciola, Filaria, Schistosoma, Strongyloides, Toxocara, Trichinella); fungal (dermatophytes, Candida)
Contact allergy Latex, pollen, animal saliva, nettle plants, caterpillars
Transfusion reactions Blood, blood products, or IV immunoglobulin administration

From Lasley MV, Kennedy MS, Altman LC: Urticaria and angioedema. In Altman LC, Becker JW, Williams PV, editors: Allergy in primary care, Philadelphia, 2000, WB Saunders, p 232.

Table 142-2 ETIOLOGY OF CHRONIC URTICARIA

Idiopathic 75-90% of chronic urticaria cases are idiopathic, and 35-40% have immunoglobulin (Ig) G, anti-IgE, and anti-FcεRI (high-affinity IgE receptor α chain) autoantibodies
Physical Dermatographism
Cholinergic urticaria
Cold urticaria
Delayed pressure urticaria
Solar urticaria
Vibratory urticaria
Aquagenic urticaria
Rheumatologic Systemic lupus erythematosus
Juvenile rheumatoid arthritis
Endocrine Hyperthyroidism
Hypothyroidism
Neoplastic Lymphoma
Mastocytosis
Leukemia
Angioedema Hereditary angioedema (autosomal dominant inherited deficiency of C1-esterase inhibitor)
Acquired angioedema
Angiotensin-converting enzyme inhibitors

From Lasley MV, Kennedy MS, Altman LC: Urticaria and angioedema. In Altman LC, Becker JW, Williams PV, editors: Allergy in primary care, Philadelphia, 2000, WB Saunders, p 234.

Urticaria can also be classified according to the temporal relationship with a stimulus and the duration of a typical hive. Lesions that last 1-2 hr are typical of the physical urticarias, in which an inciting stimulus is only briefly encountered. There is prompt mast cell degranulation, and biopsy of these lesions reveals little or no cellular infiltrate. A second form of urticaria can occur spontaneously and last 6-36 hr. These lesions typically have a prominent cellular infiltrate and can be found with food or drug reactions, chronic idiopathic urticaria, chronic autoimmune urticaria, and delayed pressure urticaria. Serum sickness reactions can be seen as a manifestation of drug reactions, and biopsy reveals a small-vessel cutaneous vasculitis. Urticaria in association with systemic lupus erythematosus or other vasculitides appears similar.

Atypical aspects of the gross appearance of the hives or associated symptoms should heighten concern that the urticaria or angioedema may be the manifestation of a systemic disease process. Lesions that burn more than itch, last >24 hr, do not blanch, or are associated with bleeding into the skin (purpura) suggest urticarial vasculitis.

Physical Urticaria

Physically induced urticaria and angioedema share the common property of being induced by environmental factors, such as a change in temperature or direct stimulation of the skin with pressure, stroking, vibration, or light (Table 142-3).

Table 142-3 DIAGNOSTIC TESTING FOR URTICARIA AND ANGIOEDEMA

DIAGNOSIS DIAGNOSTIC TESTING
Food and drug reactions Elimination of offending agent, skin testing, and challenge with suspected foods
Autoimmune urticaria Autologous serum skin test; anti-thyroid antibodies
Thyroiditis Thyroid-stimulating hormone; anti-thyroid antibodies
Infections Appropriate cultures or serology
Collagen vascular diseases and cutaneous vasculitis Skin biopsy, CH50, C1q, C4, C3, factor B, immunofluorescence of tissues, antinuclear antibodies, cryoglobulins
Malignancy with angioedema CH50, C1q, C4, C1-INH determinations
Cold urticaria Ice cube test
Solar urticaria Exposure to defined wavelengths of light, red blood cell protoporphyrin, fecal protoporphyrin, and coproporphyrin
Dermatographism Stroking with narrow object (e.g., tongue blade, fingernail)
Pressure urticaria Application of pressure for defined time and intensity
Vibratory urticaria Vibration for 4 min
Aquagenic urticaria Challenge with tap water at various temperatures
Urticaria pigmentosa Skin biopsy, test for dermographism
Hereditary angioedema C4, C2, CH50, C1-INH testing by protein and function
Familial cold urticaria Challenge by cold exposure, measurement of temperature, white blood cell count, erythrocyte sedimentation rate, and skin biopsy
C3b inactivator deficiency C3, factor B, C3b inactivator determinations
Chronic idiopathic urticaria Skin biopsy, immunofluorescence (negative result), autologous skin test
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