Thank you for your inquiry.
You have two salient questions. There is no definitive answer to each, and the strategy that one takes is clearly based on clinical judgment. Before answering, however, I would like to parenthetically mention that systemic mastocytosis without cutaneous involvement would be very rare in a 3 year-old. One thing I would do, if you have not already had the opportunity of doing it, is search his skin for any lesion suggestive of urticaria pigmentosa. If one is found, it would be an easily biopsiable lesion and if positive would eliminate the need for a bone marrow. If no lesion is found, in answer to your direct question, I would order a blood test for the 816V mutation at this time. If positive I would do a bone marrow. If negative I would continue observation and repeat serum tryptase measurements over the next couple of years at six month intervals to see if there is a rise. Serum tryptase values do not tend to increase with age. If episodes persist and the tryptase remains elevated I would do a bone marrow.
The issue as to whether or not to institute venom immunotherapy also is debatable. Of course, the positive tests could indicate sensitization without clinical reactivity. In addition, the lack of any cutaneous manifestations makes it difficult to interpret whether or not the reactions that the child experienced were truly IgE-mediated. You could certainly use the serum specific IgE to select antigens without proceeding to skin testing, but since skin tests are the “test of choice” and are considered more sensitive, you could also do skin testing only to those tests which were negative on in vitro testing.
Finally, I would treat with all venoms to which a positive test was demonstrated.
I would look diligently for any skin lesion suggestive of urticaria pigmentosa and biopsy such a lesion if present.
I would not at this time pursue a bone marrow at this time unless the 816v mutation was present, but would measure serial serum tryptase values over at least the next year or two to see if there is a rise (or persistent elevation).
Although it is debatable as to whether or not this child is a candidate for immunotherapy, I personally would initiate immunotherapy. This can be done using the in vitro test, but I would strongly consider doing skin tests for any venom that was negative on in vitro testing.
I would treat with any venom to which the child demonstrated a positive reaction.
Finally, again parenthetically, perhaps the most controversial strategy would be the decision to pursue immunotherapy. As you know, cutaneous/subcutaneous manifestations would not normally be treated in this child, so the decision to initiate immunotherapy would have to be based upon his episode of syncope. And, although syncope alone would be an unusual manifestation of a systemic response in a child this age, based upon the positive test to venom, one could not rule out an anaphylactic episode.
Thank you again for your inquiry and we hope this response is helpful to you.
Phil Lieberman, M.D.