prostaglandin-d2 and Mastocytosis--Systemic

Systemic mastocytosis is characterized by an abnormal proliferation of tissue mast cells. Symptoms of mastocytosis are primarily attributed to the release of mast cell mediators during episodes of systemic activation of the excessive numbers of mast cells. Thus, biochemical evidence for the release of increased quantities of mast cell secretory products can suggest or confirm, depending on the clinical situation, a diagnosis of systemic mastocytosis. A major advantage of the biochemical approach to the diagnosis of systemic mast cell disease is that it has allowed the recognition of a class of patients in whom episodes of systemic mastocyte activation can be unequivocally documented biochemically but in whom clear-cut evidence of abnormal mast cell proliferation is lacking by current histologic criteria. Although the release of increased quantities of mast cell mediators can be demonstrated during episodes of mast cell activation in such patients, mediator levels are usually normal at quiescent times. By contrast, patients with proliferative mast cell disease (mastocytosis) usually exhibit chronic overproduction of mast cell mediators. Mast cell secretory products that can be measured in an attempt to obtain biochemical evidence of systemic mast cell activation include histamine, prostaglandin D2, tryptase, and heparin. The analytical approaches to assessing release of those individual mast cell products are evaluated. In general, the diagnosis and investigation of patients with systemic mast cell activation can best be accomplished by concerted use of histologic examination of key tissues together with analysis of chemical markers of the mast cell.

Topics: Flushing; Heparin; Histamine; Humans; Mastocytosis, Systemic; Prostaglandin D2; Tryptases

Systemic mast cell activation disease (MCAD) is characterized by an enhanced release of mast cell-derived mediators, including eicosanoids, which induce a broad spectrum of clinical symptoms. Accordingly, the diagnostic algorithm of MCAD presupposes the proof of increased mast cell mediator release, but only a few mediators are currently established as routine laboratory parameters. We thus initiated an explorative study to evaluate in vitro typing of individual eicosanoid pattern of peripheral blood leukocytes (PBLs) as a new diagnostic tool in MCAD.. Using the "functional eicosanoid testing and typing" (FET) assay, we investigated the balance (i.e. the complex pattern of formation, release and mutual interaction) of prostaglandin E2 (PGE2) and peptido-leukotrienes (pLT) release from PBLs of 22 MCAD patients and 20 healthy individuals. FET algorithms thereby consider both basal and arachidonic acid (AA)-, acetylsalicylic acid (ASA)-, and substance P (SP)-triggered release of PGE2 and pLT. The FET assay was further supplemented by analyzing prostaglandin D2 (PGD2), as mast cell-specific eicosanoid.. We observed marked PGE2-pLT imbalances for PBLs of MCAD patients, as indicated by a markedly enhanced mean FET value of 1.75 ± 0.356 (range: 1.14-2.36), compared to 0.53 ± 0.119 (range: 0.36-0.75) for healthy individuals. In addition, mean PGD2 release from PBLs of MCAD patients was significantly, 6.6-fold higher than from PBLs of healthy individuals (946 ± 302.2 pg/ml versus 142 ± 47.8 pg/ml; P < 0.001). In contrast to healthy individuals, PGD2 release from PBLs of MCAD patients was markedly triggered by SP (mean: 1896 ± 389.7 pg/ml; P < 0.001), whereas AA and ASA caused individually varying effects on both PGD2 and pLT release.. The new in-vitro FET assay, supplemented with analysis of PGD2, demonstrated that the individual patterns of eicosanoid release from PBLs can unambiguously distinguish MCAD patients from healthy individuals. Notably, in our analyses, the FET value and both basal and triggered PGD2 levels were not significantly affected by MCAD-specific medication. Thus, this approach may serve as an in-vitro diagnostic tool to estimate mast cell activity and to support individualized therapeutic decision processes for patients suffering from MCAD.

Topics: Adult; Aged; Algorithms; Blood Chemical Analysis; Case-Control Studies; Diagnostic Tests, Routine; Eicosanoids; Female; Humans; Leukocytes; Leukotrienes; Male; Mastocytosis, Systemic; Middle Aged; Prostaglandin D2; Young Adult

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.. 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.. 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.. 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.

Topics: Aspirin; Dinoprost; Drug Administration Schedule; Humans; Mastocytosis, Systemic; Platelet Aggregation Inhibitors; Prostaglandin D2