This study will explore the possible cause of unexplained, or idiopathic, anaphylaxis. Anaphylaxis is a rapid, life-threatening, severe reaction that occurs suddenly after contact with an allergy-causing substance, usually a particular food, drug or stinging insect. The allergen triggers mast cells to release several substances, including histamine. Histamine is responsible for many of the symptoms that may occur, such as flushing, hives, swelling of the palms and soles or tongue and vocal cords, nasal congestion, itching and tearing of the eyes, shortness of breath and wheezing, stomach pain, vomiting, low blood pressure, loss of consciousness, shock, and, rarely, death. Severe episodes of anaphylaxis are treated with epinephrine (adrenaline), followed by oral antihistamines and steroids. In more than half of cases of anaphylaxis, a clear cause is not identified. These cases are called idiopathic anaphylaxis. There is no cure or long-term preventive therapy for patients with recurrent episodes of idiopathic anaphylaxis.
People between 18 and 55 years of age who have idiopathic anaphylaxis episodes at least 6 times a year (with at least one episode every 3 months) may be eligible for this study.
Participants are evaluated at the NIH Clinical Center with the following tests and procedures:
- Medical history, physical examination and blood tests.
- Bone marrow biopsy. For this test, the skin over the hipbone and the outer surface of the hipbone itself are numbed with local anesthesia. Then, a needle is inserted into the hipbone and a small amount of bone marrow is drawn into a syringe. The needle also cuts a small core of bone marrow, which is removed for analysis.
- Other tests that may be needed for evaluation of the patient's condition.
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Anaphylaxis is a severe life-threatening systemic hypersensitivity reaction resulting from the release of mediators from mast cells and basophils, and is characterized by the presence of cutaneous, respiratory, cardiovascular, or gastrointestinal signs and symptoms. Although the most common causes of anaphylaxis are reactions to foods, pharmaceutical agents, and stinging insects, a causative factor is not identified in up to 50% of individuals with recurrent anaphylaxis. These individuals are thus said to have idiopathic anaphylaxis (IA). The mechanistic cause of IA remains uncertain, although elevated levels of urinary histamine, plasma histamine, and serum tryptase are consistent with mast cell activation.
This protocol will focus on the pathogenesis of IA. Subjects 16-70 years old with episodes of unexplained anaphylaxis will be evaluated in order to correlate both clinical and laboratory features that are typical of idiopathic anaphylaxis to identify genetic and molecular pathways that may predispose to these events and to determine signaling abnormalities in mast cells. We plan to enroll up to 100 subjects in this study. We anticipate that our findings will be a first step toward the development of novel targeted therapies.