Shock syndrome associated with mastocytosis: pharmacologic reversal of the acute episode and therapeutic prevention of recurrent attacks.

: Patients with mastocytosis at times experience spontaneous episodes of severe flushing and vasodilatory shock. Antihistamine therapy has not been found to prevent uniformly the recurrence of such attacks or reverse the hypotension during the acute episode when given intravenously. We previously found marked overproduction of prostaglandin D2 in two patients with mastocytosis. This suggested the possibility that prostaglandin D2 may be an important mediator in addition to histamine in mastocytosis. We have now generalized our initial findings and have found an increased production of prostaglandin D2 ranging from 1.5-to 32.6-fold in eight additional patients with severe episodes of flushing associated with mastocytosis. In one of those patients, the release of prostaglandin D2 was found to increase approximately 81-fold during an attack of flushing. Without exception, chronic combined therapy with antihistamines and the prostaglandin biosynthesis inhibitor, aspirin, has successfully prevented the recurrence of such severe attacks in these patients, further implicating prostaglandin D2 as an important mediator. The immediate treatment of an acute hypotensive episode, however, represents a different therapeutic situation. We recently observed a severe hypotensive episode in a hospitalized patient with mastocytosis being treated with an H1 receptor antagonist alone. The hypotension was found to be refractory to intravenous fluids, dopamine, and antihistamines, but was immediately reversed by intravenous epinephrine. The self-administration of subcutaneous epinephrine during episodes of flushing in other patients has also been found to ameliorate the flushing rapidly. The apparent unique effectiveness of epinephrine in this situation may derive from an ability of epinephrine to inhibit mast-cell mediator release as a result of beta-adrenergic receptor activation.