Research > Featured Articles > Bone Marrow, Mastocytosis & Anaphylaxis
Bone Marrow, Mastocytosis & Anaphylaxis
- Nancy Gould, Former Research Committee Member
- Regis (Gigi) Park, Former Research Committee Chair
| ABSTRACT
Occult bone marrow mastocytosis presenting as recurrent systemic anaphylaxis C Akin, D Metcalfe: Laboratory of Allergic Diseases, NIAID, NIH, Bethesda MD. Journal of Allergy and Clinical Immunology Feb 2003 p S206 Unexplained episodes of recurrent anaphylaxis can be variably observed in patients with mastocytosis. Clinical characteristics of patients with mastocytosis who experience recurrent anaphylaxis, however, have not been analysed. We have thus studied thirty consecutive patients evaluated at the NIH Clinical Center with a diagnosis of systemic mastocytosis. Thirty percent of the patients (9 total; 6 males, 3 females) had a history of recurrent unexplained anaphylaxis. Seven of 9 patients (78%) with anaphylaxis lacked any cutaneous lesions of mastocytosis. This finding was significantly different than the group without anaphylaxis where only 4 of 21 (20%) lacked skin lesions (p<0.005, Fisher’s exact probability). Furthermore, patients with anaphylaxis had significantly less bone marrow involvement with mast cells. Thus, six of 9 (67%) of the patients with anaphylaxis lacked the characteristic compact mast cell aggregates in bone marrow biopsy as opposed to only 3 of 15 (20%) patients without anaphylaxis p<0.02). Five patients with anaphylaxis had neither skin lesions nor characteristic infiltrates of mast cells in bone marrow biopsy and had baseline serum tryptase levels of less than 20 ng/ml. These patients, however, had other diagnostic features of disease such as aberrant mast cell morphology, expression of CD2 and CD25 by mast cells, and the presence of codon 816 c-kit mutations. Such patients are termed to have "occult bone marrow" mastocytosis which is detectable by sensitive diagnostic approaches. In conclusion, systemic mastocytosis may be an underlying pathology in unexplained recurrent anaphylaxis in more patients than previously recognized. |
Among people who have mast cell disorders, and physicians who see such patients, the observation is sometimes made that there seems to be a basic difference between those for whom anaphylaxis is a frequent symptom and those for whom anaphylaxis is rare or has not occurred. Drs. Akin and Metcalfe and their National Institutes of Health team have looked at the similarities and differences between these two groups in 30 patients. The above abstract is a brief report of their findings, which we will describe in less technical language. This study may have important implications for patients currently diagnosed with unexplained anaphylaxis, or idiopathic anaphylaxis, as it has been referred to in clinical settings.
In this study population of 30 patients, 9 experienced repeated episodes of unexplained anaphylaxis (we will refer to those patients as “shockers”). They were compared in several ways with the 21 patients for whom anaphylaxis was not a frequent symptom (we will refer to those patients as “non-shockers”).
SKIN LESIONS ARE LESS COMMON IN “SHOCKERS”
Only two of the 9 “shockers” had mastocytosis skin lesions, such as urticaria pigmentosa. By comparison, a large majority (17 out of 21) of the “non-shockers” had mastocytosis skin lesions.
MAST CELL CLUSTERS ARE LESS COMMONLY FOUND IN THE BONE MARROW BIOPSY OF “SHOCKERS”
Six out of the 9 “shockers” did not have the mast cell clusters usually seen in bone marrow biopsy tissue in systemic mastocytosis. Compare this with the non-shockers, where all but 3 did have clusters of mast cells in their bone marrow.
In fact, 5 of the “shockers” had none of the most common findings reported in systemic mastocytosis. These 5 did not have skin lesions, they did not have mast cell clusters in their bone marrow biopsy tissue, and they did not have a serum tryptase level above 20ng/ml.
Nevertheless, they did meet minor diagnostic criteria found in the recently published consensus document on the diagnosis of systemic mastocytosis (See Table A), these being:
1. The mast cells in their bone marrow biopsy tissue had abnormal shapes.
2. In their bone marrow aspirate, some mast cells had CD2 and/or CD25 on their surface.
3. The usual mastocytosis mutation was found at the 816th amino acid in the c-kit receptor molecule on some mast cells from their bone marrow aspirate.
Because of these results, it was possible to apply the diagnosis of occult bone marrow mastocytosis to these five patients.
WHAT DOES THIS FINDING MEAN TO PEOPLE WITH UNEXPLAINED ANAPHYLAXIS?
Some people with the diagnosis of idiopathic anaphylaxis also seem to have other symptoms of systemic mastocytosis. They respond to the usual mastocytosis medications, but the commercially-available tests have not been diagnostic of mastocytosis. It now appears that some of these patients may have occult bone marrow mastocytosis, a previously unrecognised type of systemic mast cell disease.
Unfortunately, at this time only the laboratory at the National Institutes of Health in Bethesda, Maryland, and a very few research laboratories in the rest of the world, are doing the required testing in research settings to make the diagnosis of occult bone marrow mastocytosis. Because of the technical complexity involved, no commercial laboratories are presently prepared to do all the required studies. As research continues, we hope to see this situation change.
Table A. CONSENSUS CRITERIA FOR THE DIAGNOSIS OF SYSTEMIC MASTOCYTOSIS Major criteria
If one major and one minor criterion are found or if three minor criteria are found, then the diagnosis is systemic mastocytosis. |
The authors wish to thank Dr. Cem Akin of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, for his review of this article.