A Study of Histamine in Myeloproliferative Disease

1. Whole blood histamine content was measured in 80 patients with myeloproliferative disease. Increased levels were found in 60 per cent of patientswith uncontrolled polycythemia vera, in 7 per cent of patients with polycythemia vera being controlled by myelosuppressive therapy, and in 71 percent of a group with "spent" polycythemia, myeloid metaplasia and myelofibrosis.

2. The excretion of histamine in the urine was measured in 60 patients,30 with elevated blood histamine and 30 with normal blood histamine. Theurine findings paralleled the blood findings in 90 per cent of the cases.

3. Measurements of cell-poor and cell-rich fractions of blood showed thatthe histamine is contained in the white cell fraction. Elevated basophil countswere present in 50 per cent of the patients and occurred with the greatestfrequency in the groups with elevated blood and urine histamine. A roughcorrelation between the basophil count and the histamine content of bloodand white cell fractions was observed in normal subjects and most cases withmyeloproliferative disease. Data obtained in some cases of myeloproliferativedisease suggest that the histamine content of the basophil may be abnormaland that other granulocytes may contribute to the total leukocyte histamine.

4. Myelosuppressive agents produced a reduction in histamine (expressedper 10⁹ myeloid cells) and a decrease in urine histamine as control of themyeloproliferative process was achieved. Treatment with phlebotomy aloneproduced no change in histamine levels.

5. The incidence of pruritus, upper gastrointestinal distress and urticarialmanifestations was increased 7-fold, 4-fold and 12-fold, respectively, in patients with elevated histamine levels as compared with those who had normalhistamine levels.

6. Cyproheptadine, a potent antihistaminic, successfully controlled pruritus,relieved pyrosis and suppressed urticarial eruptions in patients with elevatedhistamine levels. Suppression of the reaction to subcutaneously administeredcodeine (a histamine-releaser) afforded objective evidence that cyproheptadine blocked the effects of histamine release in vivo.

7. The metabolism of histamine and the role of elevated histamine levelsin the clinical manifestations and pathophysiology of myeloproliferative diseaseare discussed.

Submitted on September 23, 1965 Accepted on May 24, 1966