Urticaria is a common skin disorder that is classified according to its chronicity into acute and chronic forms. It may occur spontaneously or on exposure to a physical factor. In the latter case, the urticaria is classified as a "physical urticaria". Physical urticaria may be induced by mechanical and applied pressure, exercise, or exposure to cold, heat, sun, water, or vibration. The urticarial lesions are generally thought to be the result of mast cell activation and degranulation, which is supported by the finding of increased levels of serum histamine during some urticarial flares. Passive transfer experiments, whereupon serum from affected donors is transferred into recipient's skin followed by physical stimulation with resultant urticaria at the site of challenge, have been positive in some instances. This suggests the presence of an intrinsic factor in serum, such as IgE, which then mediates activation of tissue mast cells. However, the pathogenesis in general remains unclear and a genetic basis for these disorders has not been elucidated.

Recently, the genetic basis for an autoinflammatory syndrome characterized by cold induced urticarial lesions along with fevers and joint inflammation has been found, These patients have mutations in the cold-induced autoinflammatory syndrome t (CIASI) gene that encodes a protein called cryopyrin. Cryopyrin is part of a multiprotein complex termed the inflammasome that regulates IL-1 beta production, and plays a critical role in innate immunity. In Schnitzler's syndrome, another autoinflammatory disorder, patients present with chronic urticaria and monoclonal gammopathy. These patients and those with cryopyrinopathies respond dramatically with IL-1beta antagonist therapy.

The focus of this protocol will be to determine the role of the inflammasome and mast cell activation in the pathogenesis of physical induced urticaria. Subjects will undergo a clinical evaluation that will include verification of their urticaria. Blood and tissue samples, if available, will be collected for analysis. The analysis will be targeted toward the determination of IL-1beta and other cytokine levels, screening for mutations in the inflammasome, gene expression studies and immunohistochemistry in tissue samples. In addition, a search for levels of expression of mast cell activating proteins and sequencing for polymorphisms may be incorporated.

Urticaria is a common skin disorder that is classified according to its chronicity into acute and chronic forms. It may occur spontaneously or on exposure to a physical factor. In the latter case, the urticaria is classified as a "physical urticaria". Physical urticaria may be induced by mechanical and applied pressure, exercise, or exposure to cold, heat, sun, water, or vibration. The urticarial lesions are generally thought to be the result of mast cell activation and degranulation, which is supported by the finding of increased levels of serum histamine during some urticarial flares. Passive transfer experiments, whereupon serum from affected donors is transferred into recipient's skin followed by physical stimulation with resultant urticaria at the site of challenge, have been positive in some instances. This suggests the presence of an intrinsic factor in serum, such as IgE, which then mediates activation of tissue mast cells. However, the pathogenesis in general remains unclear and a genetic basis for these disorders has not been elucidated.

Recently, the genetic basis for an autoinflammatory syndrome characterized by cold induced urticarial lesions along with fevers and joint inflammation has been found, These patients have mutations in the cold-induced autoinflammatory syndrome t (CIASI) gene that encodes a protein called cryopyrin. Cryopyrin is part of a multiprotein complex termed the inflammasome that regulates IL-1 beta production, and plays a critical role in innate immunity. In Schnitzler's syndrome, another autoinflammatory disorder, patients present with chronic urticaria and monoclonal gammopathy. These patients and those with cryopyrinopathies respond dramatically with IL-1beta antagonist therapy.

The focus of this protocol will be to determine the role of the inflammasome and mast cell activation in the pathogenesis of physical induced urticaria. Subjects will undergo a clinical evaluation that will include verification of their urticaria. Blood and tissue samples, if available, will be collected for analysis. The analysis will be targeted toward the determination of IL-1beta and other cytokine levels, screening for mutations in the inflammasome, gene expression studies and immunohistochemistry in tissue samples. In addition, a search for levels of expression of mast cell activating proteins and sequencing for polymorphisms may be incorporated.

• INCLUSION CRITERIA:
  1. Subject must be at least 6 months of age and no older than 65 years of age.
  2. Documented history of a clinically reproducible physical urticaria in which the inciting trigger caused disease and which has been evaluated by the patient's physician, or be a non affected family member of such a patient.
  3. Letter of referral, with copies of pertinent medical history and laboratory studies, from the subject's referring physician.
  4. Ability to give informed consent.
  5. Willing to donate blood for sample storage to be used for future research.

EXCLUSION CRITERIA:

1. Presence of conditions which, in the judgment of the investigator or the referring physician, may put the subject at undue risk, such as acute infection, severe thrombocytopenia (minimum platelet count of 30,000), or significant cardiovascular disease
2. Any condition that in the view of the principal investigator (PI) would make the subject unsuitable for enrollment in this study
3. Inability to provide informed consent
4. History of HIV or other known immunodeficiency
5. History or evidence of chronic
6. Pregnancy