Q:

7/18/2013
39 year old lady presenting with flushing. Food allergy evaluation negative. Labs: normal cbc with diff, normal CMP, UA normal. Urine metanephrines normal, urine catecholamines normal. Tryptase checked 3 times: 12.9, 13.7, 15.9. She does not have a rash c/w urticaria pigmentosa. Remote history of angioedema of lips and hands after wasp sting is going for hymenoptera testing. She is currently on H1 and H2 blockers, flushing is better. With the tryptase levels being elevated but not >20, should I send her for a BM biopsy?

A:

Thank you for your inquiry.

I have copied below the abstract of an article very pertinent to your question. In this study, as you can see, the “cutoff point” for a significantly elevated serum tryptase in patients who have experienced anaphylactic reactions to hymenoptera signaling that they may have an underlying mast cell disorder was 11.7. The levels you expressed in your inquiry have been repeatedly above 11.7 and therefore, at least according to the suggestions in this article, your patient is a candidate for a bone marrow examination.

I might mention parenthetically that the workup for flush is sometimes quite frustrating, and there is a rather old but nice article that goes to the differential diagnosis of flush. For your convenience, I have also copied the abstract of this article below in case you decide to do a bone marrow and it does not show findings of mastocytosis or mast cell activating disorder.

Thank you again for your inquiry and we hope this response is helpful to you.

The Journal of Allergy and Clinical Immunology
Volume 123, Issue 3 , Pages 680-686, March 2009
Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels
Background: Anaphylaxis after Hymenoptera stings has been reported in subjects with mastocytosis, but few data exist regarding disease prevalence in populations allergic to these insects.
Objective: The incidence of clonal mast cell (MC) disorders in subjects with both systemic reactions to Hymenoptera stings and increased serum baseline tryptase (sBT) levels was assessed by using bone marrow (BM) aspirates and biopsy specimens.
Methods: Subjects with a history of a systemic reaction caused by a Hymenoptera sting underwent the standard diagnostic work-up for Hymenoptera allergy, and sBT levels were measured. Subjects with an increased sBT level had BM evaluation that included histology/cytology, flow cytometry, and detection of KIT mutations.
Results: Forty-four (11.6%) of 379 subjects with systemic reactions had increased sBT levels (>11.4 ng/mL), and 31 (70.5%) of these had a history of anaphylaxis. Thirty-four subjects with increased sBT levels underwent a BM analysis. Histology detected diagnostic or subdiagnostic MC infiltrates in 22 (65%) of 34 patients. Abnormal MCs were identified by means of flow cytometry and cytology in 26 (78.8%) of 33 and 20 (58.8%) of 34 subjects, respectively. A KIT mutation was detected in 17 (54.8%) of 31 subjects. The diagnosis was indolent systemic mastocytosis in 21 (61.7%) of 34 subjects and monoclonal MC activation syndrome in 9 (26.5%) of 34 subjects. All subjects with anaphylaxis had one of those 2 disorders.
Conclusion: The concomitant presence of systemic reactions (especially anaphylaxis) after Hymenoptera stings and increased sBT levels strongly suggests that a BM examination is indicated for the diagnosis of clonal MC disease.

The Journal of Allergy and Clinical Immunology
Volume 93, Issue 1, Part 1 , Pages 53-60, January 1994
A clinicopathologic study of ten patients with recurrent unexplained flushing
Abstract
We describe the clinicopathologic features of 10 patients with recurrent unexplained flushing. These patients were referred to the National Institutes of Health with a diagnosis of mastocytosis or idiopathic anaphylaxis. Both diagnoses were eliminated after evaluation. Patients reported attacks of flushing lasting 15 minutes to 2 days and associated with such symptoms as anxiety, chest tightness, paresthesia, slurred speech, weakness, and pruritus. Abdominal pain was a constant feature, often associated with cramping and an increase in stool frequency. Attacks witnessed by physicians consisted of an exaggerated blush response of the face and upper part of the chest, and were sometimes associated with tachycardia, mild hypertension, and tachypnea. Hives, angioedema, wheezing, and hypotension were not observed. Routine laboratory studies and 5-hydroxyindoleacetic acid, vanillylmandelic acid, and plasma histamine levels were normal. Plasma histamine levels did not elevate during attacks. When performed, results of bone marrow examinations, skin biopsies, and bone scans were normal. Psychiatric examinations frequently revealed somatization disorders. Patients had often been prescribed a wide variety of medications including antihistamines, nonsteroidal anti-inflammatory drugs, and steroids, with little or no benefit. Despite the benign nature of the clinical and laboratory findings, patients had undergone repeated, often invasive, examinations for several years. Whether such patients have a prominent flush response exaggerated through a somatization disorder or a relatively benign flushing disorder associated with putative mediator release remains to be determined. Recognition of this category of patients with unexplained flushing will avoid subjecting such patients to unwarranted repeated examinations, procedures, and inappropriate therapy.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology