Background: * Urticaria is a common itchy skin disorder that may occur spontaneously or on exposure to a physical trigger (called physical urticaria). * Researchers are studying the genetic basis of a physically induced urticarial syndrome. Once called familial cold urticaria, this condition is now called familial cold autoinflammatory syndrome (FCAS). FCAS is an autoinflammatory disease, a group of inherited disorders characterized by unprovoked episodes of inflammation. Patients with FCAS often have hives, joint pain, and fever following general exposure to cold. * Patients with FCAS have a mutation in a gene that makes a protein called cryopyrin. Cryopyrin seems to be involved with the production of a proinflammatory mediator called interleukin-1 (IL-1). Patients with FCAS and others with autoinflammatory syndromes have benefited from medication that blocks the effects of IL-1. Objectives: * To investigate mechanisms that may cause physical hives or urticaria. * To reproduce urticaria through challenge testing (procedures to test the skin for a reaction to a stimulus), followed by mast cell studies, measurement of IL-1, genetic studies, and other molecular studies to lead to a better understanding of urticaria and to design safe and more effective treatments. Eligibility: * Patients between 6 months and 65 years of age with a documented history of clinically reproducible physical urticaria that triggers hives and that has been evaluated by a physician. Patients should have a letter of referral, including copies of pertinent medical history and laboratory studies, from a referring physician. * Affected and nonaffected family members of such patients. * Exclusion criteria include (1) the presence of conditions that may put the subject at undue risk, such as acute infection, severe thrombocytopenia (a lower than normal number of platelets in the blood), or significant cardiovascular disease; (2) any condition that would make the subject unsuitable for enrollment in this study; and (3) a history of HIV, other known immunodeficiency, or evidence of chronic Hepatitis B and/or C infection. Design: * Researchers will conduct the following tests to verify which triggers cause the hives: * History and physical exam to determine the relationship between the trigger and appearance of the hives. * Blood samples for baseline screening (additional samples may be taken within 8 hours of triggering hives). * Verification of hives using standard challenge testing. * Procedures to trigger urticaria (the challenge testing) include dermatographism (stroking the skin), delayed pressure urticaria (direct pressure), cold-induced urticaria (cold exposure), cholinergic urticaria (exercise, hot water), solar urticaria (sun exposure), localized heat urticaria (direct heat exposure), aquagenic urticaria (room temperature water), and vibratory angioedema (direct vibratory stimulus exposure). * Participants who have a positive history for hives and failed challenge testing (that is, hives resulted from the triggers) will be asked to provide a skin biopsy and additional bloods samples for research purposes. * Participants will be asked to return to the clinic within 1 month if multiple triggers could not be verified during the initial visit, or to return for additional research evaluations, which may include a skin punch biopsy and blood sample collection. Patients may have to stay at the hospital overnight, if required to document the disease. * Nonaffected family members who enroll in this protocol will provide samples for comparison with the family member who has a history of hives. * Participants will receive a small financial compensation for the skin biopsy.
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. The goal of this protocol is thus to gain a better understanding of the pathogenesis of physical urticaria through the investigation of subjects with severe and unusual phenotypes and/or inherited patterns of disease. 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 novel serum mediators, mast cell activation and mutational analysis in families with inherited patterns.
Study Type
OBSERVATIONAL
Enrollment
173
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
to determine the role of mast cell activation and genetic predisposition in the pathogenesis of physically induced urticaria.
The patient s physical urticaria will be verified through standard testing.
Time frame: 12/31/2028
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.