Answer:
I am grateful to Dr. Cem Akin who provided the following response with references. The most common cause of an elevated baseline tryptase level in a patient whose bone marrow biopsy did not show any evidence of mastocytosis is hereditary alpha tryptasemia (HAT) (1). This is a rather common genetic variant of uncertain significance observed in up to 6% of population and is inherited in an autosomal dominant pattern. The cause of HAT is duplication or multiplication of the alpha tryptase gene encoded by TPSAB1 locus (genotyping testing available from Gene by Gene, Houston, TX). The tryptase elevation reflects a gene dosage effect. The initial publication reporting HAT reported possible correlations with a number of diverse clinical symptoms including itching, IBS-like symptoms and hypermobility and dysautonomia but these observations need to be confirmed in larger cohorts. Furthermore, there is no evidence that these individuals have increased secretion of other mast cell mediators, and some remain completely asymptomatic. Since the effect of HAT on disease phenotype is not clear at this time, it is difficult to recommend treatment based on this finding alone.
In this patient, the plasma histamine level is difficult to interpret as it can be derived from blood basophils and may be influenced by sample processing. Therefore, I would not recommend linking this increased level to his elevated tryptase. Likewise, in a patient without hives, the utility of omalizumab would be unpredictable. I would recommend looking for other causes of chronic itching in this patient including neurogenic, dermatologic, and others. A trial of H1 and H2 antihistamines would be reasonable from risk to benefit ratio standpoint.
Other causes of elevated tryptase include chronic renal insufficiency and myeloid neoplasias but these would have been detected in bone marrow exam and routine bloodwork (2).
References:
1. Lyons JJ, Yu X, Hughes JD, Le QT, Jamil A, Bai Y, Ho N, Zhao M, Liu Y, O'Connell MP, Trivedi NN, Nelson C, DiMaggio T, Jones N, Matthews H, Lewis KL, Oler AJ, Carlson RJ, Arkwright PD, Hong C, Agama S, Wilson TM, Tucker S, Zhang Y, McElwee JJ, Pao M, Glover SC, Rothenberg ME, Hohman RJ, Stone KD, Caughey GH, Heller T, Metcalfe DD, Biesecker LG, Schwartz LB, Milner JD. Elevated basal serum tryptase identifies a multisystem disorder associated with increased TPSAB1 copy number.
Nat Genet. 2016 Dec;48(12):1564-1569.
2. Schwartz LB. Diagnostic value of tryptase in anaphylaxis and mastocytosis.
Immunol Allergy Clin North Am. 2006 Aug;26(3):451-63.
I hope this information is helpful.
Jacqueline A. Pongracic, MD, FAAAAI