Bethesda, Maryland 20892

  • Familial Cold Autoinflammatory Syndrome

Purpose:

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.


Study summary:

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.


Criteria:

- INCLUSION CRITERIA: Affected subjects/guardian must: 1. Be at least 2 years of age and no older than 90 years of age. 2. Have a history of a physical urticaria, which has been evaluated by the patient's healthcare practitioner. 3. Provide copies of pertinent medical history and laboratory studies. 4. Have a health care provider outside of NIH. 5. Be willing to give informed consent. 6. Be willing to donate blood for sample storage to be used for future research. Non-affected relatives/guardian must: 1. Be at least 2 years of age and no older than 90 years of age. 2. Have a relative who is enrolled on this protocol and is known to have documented history of a physical urticaria. 3. Not have a history of physical urticaria. 4. Be willing to give informed consent. 5. Be willing to donate blood for sample storage to be used for future research. Normal volunteers must: 1. Be 18-65 years of age. 2. Be non-atopic (not have a history of allergic rhinitis, asthma, atopic dermatitis) per subject s medical history. 3. Have the ability to give informed consent. 4. Be willing to donate blood for sample storage to be used for future research. 5. Not have a history of physical urticaria. EXCLUSION CRITERIA: The following criteria apply to all subjects: 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. History of HIV or other known immunodeficiency 4. History or evidence of chronic Hepatitis B and/or C infection 5. Pregnancy


NCT ID:

NCT00887939


Primary Contact:

Principal Investigator
Hirsh D Komarow, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)

Hye Jeong C Bolan, R.N.
Phone: (301) 594-1233
Email: bolanhy@mail.nih.gov


Backup Contact:

Email: komarowh@mail.nih.gov
Hirsh D Komarow, M.D.
Phone: (301) 594-2197


Location Contact:

Bethesda, Maryland 20892
United States

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
Phone: 800-411-1222
Email: ccopr@nih.gov

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 27, 2022

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