Thank you for your recent inquiry.
You asked several questions regarding the case. I will try to answer them as best I can.
I would not be concerned about the RA at this time. If this were a sign that there was an underlying early rheumatoid arthritis or other “autoimmune condition,” evidence will accrue for the presence of this disease over time. I do not think that any further workup to follow-up on the RA would be beneficial at this time.
Chronic urticaria is not associated with systemic elevations of tryptase in most instances. And the article you mentioned is a "little tricky" in that the levels were elevated compared to their controls, but not really elevated according to the standards we normally apply. The levels in their urticaria subjects were only 6.6 +/-4.1 mug/L. (I have copied the abstract for your convenience below.) Also, although an elevation of tryptase above 11.4 ng/mL is suggestive of mastocytosis in a patient who has experienced an anaphylactic reaction to hymenoptera (1). Without such a history, in most instances a level of 13 mcg/L would not prompt a bone marrow biopsy. And the only way to make a diagnosis of mastocytosis is to do a bone marrow biopsy, and evaluate it histologically and with surface markers (CD25) indicating the presence of a clonal mast cell disorder.
Although finding elevated histamine metabolites in the urine might push you more in the direction of mastocytosis, you would still have to do a bone marrow biopsy to confirm the diagnosis. Since your patient appears to be under reasonably good control with antihistamines, the question becomes, what additional therapy might you add if a diagnosis of mastocytosis was made. The vast majority of such cases are associated with an 816V mutation, and are not responsive to any specific therapy. Therefore it would be unlikely that you would at this time add any specific therapy to the regimen you are employing even if a diagnosis was made.
Thus at this time, I do not think I would pursue the diagnosis any further in regards to mastocytosis. I would follow the patient. If the tryptase became more highly elevated and/or if the symptoms were no longer adequately controlled by antihistamine therapy, you could reconsider performing a bone marrow biopsy.
As you know, the vast majority of cases of chronic idiopathic urticaria are just that; by “that” I mean “idiopathic.” And these cases defy attempts at diagnosis. Markers such as a positive CU index simply indicate that an IgG antibody may be playing a role in the pathogenesis. They actually do not alter your therapy or affect the patient’s course.
I might parenthetically mention one thing. You described “crusting skin lesions.” This of course would not be consistent with urticaria. I have no ready explanation for this unless they are related to scratching with subsequent infection. They also would not normally be consistent with mastocytosis to my knowledge. So I am puzzled by the statement “no unusual skin lesions” because “ulcers” and “skin crusts” would not normally be found in urticaria. I do not have a ready explanation for these.
In summary, at this time, I do not think that I would pursue the diagnosis further. As long as he is responding reasonably well to antihistamines, and the tryptase does not increase significantly, I would simply continue to treat him symptomatically. But I would pursue the “ulcers” and “skin crusting” if they are prominent features of his condition.
Thank you again for your inquiry and we hope this response is helpful to you.
Clin Exp Allergy. 2010 Aug 16. [Epub ahead of print]
Serum total tryptase levels are increased in patients with active chronic urticaria.
Ferrer M, Nuñez-Córdoba JM, Luquin E, Grattan CE, De la Borbolla JM, Sanz ML, Schwartz LB.
Department of Allergy and Clinical Immunology, Clínica Universidad de Navarra Medical School, Pamplona, Spain.
Summary Background We have demonstrated previously mast cell histamine release upon incubation with chronic urticaria (CU) sera, presumably by degranulation. Objective To explore total and mature tryptase in order to assess whether any increase in total tryptase levels is due in part to mast cell degranulation or to mast cell burden. We also wanted to explore differences between the autoimmune groups called idiopathic (serum unable to activate basophils), and to correlate total and mature tryptase levels with different urticaria features. Methods We measured total and mature tryptase serum levels in 81 CU patients, 16 atopic donors and 21 healthy control sera. We assessed autoimmunity by measuring the CD63 expression in normal basophil donors upon incubation with CU sera. Results We found significantly higher levels of total tryptase in the sera of CU patients (6.6 +/-4.1 mug/L) than in sera from healthy non-atopic subjects (4.4 +/-2.8 mug/L) and from atopic subjects (4.5 +/-1.7 mug/L). Mature tryptase levels were undetectable (<1 ng/mL). Total tryptase levels in the autoimmune urticaria group were significantly higher (9.8 +/-5.4 mug/L) than the idiopathic urticaria group (4.4 +/-2.2 mug/L). A significant difference in total tryptase was found between symptomatic patients (7.3 +/-4.1 mug/L) compared with asymptomatic ones (5.7 +/-4.1 mug/L) at the time of venesection. No difference was found in mature tryptase levels either. Conclusion Total elevated tryptase levels are not accompanied by an elevated mature tryptase levels, as might be expected if the serum levels reflected mast cell degranulation.
Bonadonna P, et al. Clonal mast cell disorders in patients with systemic reactions to hymenoptera stings and increased serum tryptase levels. J Allergy Clin Immunol 2009; 123(3):680-686.
Phil Lieberman, M.D.