Diminished reliability of tryptase as risk indicator of mastocytosis in older overweight subjects.

BACKGROUND: Currently, measurement of serum tryptase level is the most commonly used test to estimate the need for bone marrow biopsy in patients suspected to have indolent systemic mastocytosis (ISM). Yet tryptase levels do not solely reflect the mast cell load and can be elevated by overweight, older age, and impaired renal function. The influence of these factors on urinary methylhistamine (MH) and methylimidazole acetic acid (MIMA) is still unknown. OBJECTIVE: We investigated the impact of age, body mass index (BMI), and kidney function on the diagnostic accuracy of tryptase, MH, and MIMA to select the most optimal test indicating the necessity of a bone marrow biopsy in ISM-suspected patients. METHODS: Retrospective data analysis of all adults in whom bone marrow investigations were performed because of high clinical suspicion and/or elevated tryptase, MH, or MIMA. RESULTS: 194 subjects were included. ISM was present in 112 and absent in 82 subjects (non-ISM). Tryptase was elevated by age and body weight in non-ISM subjects and by BMI in ISM subjects; however, these factors did not influence MH or MIMA. In the total study population, the diagnostic accuracy of tryptase, MH, and MIMA were comparable (area under the curve 0.80, 0.80, and 0.83). In subjects >50 years with a BMI >25 kg/m(2), the diagnostic accuracy of MIMA was higher compared with that of tryptase (area under the curve 0.93 vs 0.74; P = .011). CONCLUSION: In ISM-suspected patients >50 years with a BMI of >25 kg/m(2), MIMA has a greater value compared with tryptase in estimating the need for bone marrow biopsy.

The measurement of leukotrienes in urine as diagnostic option in systemic mastocytosis.

Clinical symptoms of patients with mastocytosis may include skin reactions, but also gastrointestinal symptoms with hyperacidity and dysmotility (e.g. ulcer, diarrhea, pain). They are mostly caused by mediators derived from activated mast cells. In order to investigate the impact of leukotrienes on the clinical symptoms excretion of leukotriene B4 (LTB4) and leukotrienes C4-D4-E4 (cysteinyl-leukotrienes) into urine was studied in 9 patients with indolent systemic mastocytosis divided into a group with high and low intensity of symptoms and in 11 healthy volunteers. Leukotriene excretion was determined by ELISA and correlated with methylhistamine excretion. Patients with systemic mastocytosis with high and low intense symptoms showed significantly higher urinary excretion of cysteinyl-leukotrienes than controls. There was a positive correlation of cysteinyl-leukotriene excretion and urinary methylhistamine excretion. LTB4 excretion was also significantly increased in patients with systemic mastocytosis compared to healthy volunteers. No correlation of urinary LTB4 excretion with urinary methylhistamine was observed. The present study demonstrates that urinary excretion of LTB4 and cysteinyl-leukotrienes LTC4-D4-E4 is clearly enhanced in indolent systemic mastocytosis Hence, determination of leukotriene excretion into urine can be used as a tool in the diagnostic and in the therapeutic monitoring of systemic mastocytosis.

Increased leukotriene E4 excretion in systemic mastocytosis.

Cysteinyl leukotrienes such as LTE(4) are produced by mast cells, neutrophils, eosinophils, and macrophages. LTE(4) levels have not been reported in systemic mastocytosis, a disorder with a large increase in mast cell numbers. Urinary LTE(4) from patients referred for symptoms potentially due to mast cell degranulation or systemic mastocytosis was measured by a commercial cysteinyl leukotriene enzyme immunoassay kit. The diagnosis of systemic mastocytosis was established using current World Health Organization criteria. Compared with a control group of patients with various potential mast cell-related symptoms (e.g., "spells"), patients with systemic mastocytosis had a significant (P=.01) increase in urinary LTE(4) excretion, whether expressed as LTE(4) ng/g creatinine or as LTE(4) ng/24h. There was a moderate correlation of LTE(4) ng/24h with excretion of N-methyl histamine and serum tryptase but not with urinary 11beta-prostaglandin F(2alpha) (11beta-PGF(2alpha)) excretion. LTE(4) excretion is increased in patients with systemic mastocytosis and potentially contributes to clinical symptoms.

Survey of aspirin administration in systemic mastocytosis.

BACKGROUND: Previous recommended doses for aspirin use in systemic mastocytosis have been 3.9-5.2g/d. Here, the aspirin doses and biochemical responses of patients with systemic mastocytosis given aspirin to decrease prostaglandin D(2) levels and prevent symptoms were reviewed. METHODS: Twenty patients with systemic mastocytosis who had been given aspirin were identified, and their clinical and laboratory records were reviewed including changes in the excretion of the prostaglandin D(2) metabolite 11beta-prostaglandin F(2alpha) in response to aspirin. RESULTS: Two of 20 patients developed either a delayed reaction or flushing during outpatient updosing with aspirin. In 20 of 20 patients with elevated baseline urinary excretion of 11beta-prostaglandin F(2alpha), aspirin therapy caused a reduction to normal levels of excretion. Doses of aspirin required ranged from 81mg twice daily to 500mg twice daily. CONCLUSIONS: Control of elevated prostaglandin D(2) levels in systemic mastocytosis can be achieved with lower doses of aspirin than previously reported as necessary in this disorder.