Blood Factors in Mastocytosis and Unexplained Anaphylaxis and Flushing
Blood Factors in Mastocytosis and Unexplained Anaphylaxis and Flushing
This study will 1) identify characteristics of bone marrow mast cells in patients with
 unexplained anaphylaxis and flushing or with mastocytosis and 2) determine whether
 mastocytosis might be the underlying cause of unexplained anaphylaxis in some patients with
 this condition. Anaphylaxis is a hypersensitivity reaction in which patients may have
 flushing, hives, stuffy nose, red itchy eyes, difficulty breathing, swelling of the tongue,
 throat, palms and soles, abdominal cramping, lightheadedness, decreased blood pressure, and
 loss of consciousness. Although allergens are a common cause of anaphylactic episodes, no
 cause can be identified in up to 50 percent of patients who have recurrent events.
 Mastocytosis is a disease of excessive mast cells in tissues such as skin and bone marrow.
 These cells can release chemicals that result in itching, blisters, flushing, bone pain, and
 abdominal pain.

 Patients 18 years of age and older who have episodes of anaphylaxis or flushing with no
 apparent cause or who have mastocytosis may be eligible for this study. Participants will
 have a medical history and physical examination; blood tests to identify genetic changes that
 are important in the growth, development, and functioning of human mast cells; and bone
 marrow aspiration and biopsy. For the bone marrow procedure, the skin over the hipbone and
 the outer surface of the bone itself are numbed with local anesthesia. Then, a special needle
 is inserted into the hipbone and about 1 tablespoon of bone marrow is drawn into a syringe.
 Another needle is inserted into the same area to collect a small piece of the bone marrow.
 Additional procedures may include allergen testing, urinalysis, and 24-hour urine collection.

 Participants will return to NIH for reassessment of disease status in 12 to 18 months. The
 follow-up evaluation will include a history and physical examination, blood tests, possible
 repeat bone marrow and aspiration in patients whose clinical signs or symptoms change
 significantly, and other tests as clinically indicated.

 First-degree relatives (parents, children, siblings) may be enrolled in limited instances to
 provide a blood sample for genetic analysis related to mast cell development and function for
 comparison with that of patients when they have similar symptoms.
Anaphylaxis is a severe systemic hypersensitivity reaction caused by release of mediators
 from mast cells and basophils. Signs and symptoms of anaphylaxis may include generalized
 flushing, hives, stuffy nose, red and itchy eyes, difficulty in breathing, swelling of the
 tongue, throat, palms and soles, gastrointestinal cramping, lightheadedness and loss of
 consciousness. Although most common causes of anaphylaxis include foods, drugs and stinging
 insects, a causative factor is not identified in up to 50% of the patients with recurrent
 anaphylactic episodes. Mast cells are important mediators of anaphylaxis. This study will
 examine the hypothesis that some patients with unexplained anaphylaxis may have systemic
 mastocytosis, a disorder of pathologic mast cell proliferation, as an underlying cause. In
 addition, it will investigate hematopoietic cells, which result in their tissue mast cells
 being more susceptible to degranulation. The study will enroll patients with mastocytosis
 with or without flushing or anaphylaxis, and patients with unexplained flushing or
 anaphylaxis. Patients will receive a clinical evaluation, blood tests and a bone marrow
 biopsy and aspirate. Research studies planned include flow cytometric analysis of blood and
 bone marrow cells, investigation of mutations or polymorphisms in genes involved in mast cell
 growth and differentiation, determination of surrogate disease markers and examination of
 mast cell growth and function. The study will improve the understanding of the mechanisms
 involved in anaphylactic reactions, which could in turn lead to development of strategies to
 better prevent or treat the episodes.
INCLUSION CRITERIA FOR PATIENTS WITH MASTOCYTOSIS:

 Age equal to or greater than 18 years.

 Diagnosis of mastocytosis established by presence of typical urticaria pigmentosa skin
 lesions or a bone marrow biopsy.

 Letter of referral from prospective study participant's local doctor.

 Ability to give informed consent.

 EXCLUSION CRITERIA FOR PATIENTS WITH MASTOCYTOSIS:

 Age less than 18 years.

 Lack of a referral physician.

 Presence of co-morbid conditions which, in the judgment of the investigator or the
 referring physician, may put the patient at undue risk for travel (such as an acute
 infection, severe thrombocytopenia).

 Inability to provide informed consent.

 Inability or refusal to undergo a bone marrow biopsy and aspirate.

 Known allergy to latex or Lidocaine.

 INCLUSION CRITERIA FOR PATIENTS WITH UNEXPLAINED FLUSHING OR ANAPHYLAXIS:

 Age equal to or greater than 18 years.

 Presence of flushing or anaphylaxis with negative workup for known causes such as carcinoid
 syndrome, pheochromocytoma, food allergy.

 Ability to give informed consent.

 EXCLUSION CRITERIA FOR PATIENTS WITH UNEXPLAINED FLUSHING OR ANAPHYLAXIS:

 Same as for patients with mastocytosis.

 Known cause for anaphylaxis or flushing.

 Frequent life-threatening anaphylactic episodes: History of 6 or more separate attacks
 resulting in ER visits in the 6 months preceding the referral.

 INCLUSION CRITERIA FOR RELATIVE:

 To have a first-degree relative accepted to the protocol as a patient with unexplained
 anaphylaxis, flushing or mastocytosis.

 Ability to give informed consent. For minors, ability of the parent to give informed
 consent.

 There are no age restrictions.