Chronic urticaria (CU) is a relatively common but vexing disease. The pathophysiology is based on the cutaneous mast cell release of mediators, predominantly
histamine. Release can be induced via specific
immunoglobulin E (
IgE), components of complement activation and nonspecifically by various compounds including endogenous
peptides,
endorphins, and
enkephalins. In >30% of CU patients, autoimmune phenomena have been found, characterized by positive autologous serum skin test,
antibodies to the alpha-subunit of the basophil
IgE receptor, to
IgE itself, and, perhaps, the most clinically relevant, thyroid autoimmunity. Studies suggest that the products of the activated immune system can lower the cutaneous mast cell release threshold, possibly allowing activation by endogenous compounds. The resulting release of mediators produces the clinical picture of recurrent
hives. Although the goal of management of CU is the identification of a treatable cause, in most CU patients, especially adults, a cause is not frequently found. Identified causes include drugs, foods,
infections,
immune complex production leading to urticarial
vasculitis,
autoantibody production, and underlying
autoimmune disease, particularly
autoimmune thyroiditis. The treatment of the
thyroiditis with suppressive doses of
thyroid hormone often results in the remission of the CU. Given the marginally effective and sometimes dangerous medical
therapy available for CU, a systematic and thorough approach to identify a treatable cause in difficult CU patients is warranted.