Studies on Histamine Metabolism in Mastocytosis

Abstract

The urinary excretion of histamine and its main metabolite, 1-methyl-4-imidazoleacetic acid (MeImAA), was determined in 30 adult patients with the clinical diagnosis of urticaria pigmentosa (UP). Clinical and laboratory investigations including skin histology, bone marrow examination, and scintigraphy of the skeleton, liver, and spleen revealed systemic manifestations in 14 cases. Among the 16 cases with dermal proliferation of mast cells only 3 cases classified as telangiectasia macularis eruptiva perstans (TMEP). All patients with systemic mastocytosis and UP excreted increased amounts of MeImAA in the urine while normal amounts were found in 2 of the patients with TMEP. A significant correlation existed between MeImAA excretion and the extent of mast cell infiltration in skin and internal organs. No such correlation was found for urinary histamine. Urinary MeImAA but not histamine is therefore considered a useful indicator of systemic involvement by reflecting the size of the mast cell histamine pool. The main symptom of the patients was pruritus, which was moderate to severe in 17 and mild or absent in 13 cases. Gastrointestinal symptoms were present in 14 patients. However, there was no obvious correlation between the excretion of MeImAA and any of the symptoms recorded. Neither was the severity of pruritus correlated to the histamine content of the skin, which was measured in both lesional and unaffected skin in 23 of the patients. Thus, symptoms possibly caused by histamine in mastocytosis patients are not directly related to urinary histamine metabolite excretion or tissue histamine content.

Cutaneous Mastocytosis in Adults

“…measurements of mast cell mediators, should be sought in mastocytosis, but random analysis of the urinary histamine levels was not proven useful for establishing the diagnosis. Only 1–3% of histamine appears unmetabolized in the urine, but there may be an increase in the major urinary histamine metabolites, N T -methyl-histamine and 1-methyl-4-imidazoleacetic acid, and the major urinary metabolite of prostaglandin D 2 [22, 23, 24]. …”

Surrogate Markers of Disease in Mastocytosis

“…Measurement of the histamine metabolites N-methylhistamine and methylimidazoleacetic acid in 24-hour urine specimens are the preferred method of assessment of baseline histamine levels in patients [9]. The levels of these metabolites appear to correlate with the amount of mast cell burden [10]. One study, however, found serum tryptase levels to be a more sensitive indicator of limited disease [11].…”

Systemic Mastocytosis

“…Patients with systemic mastocytosis appear to have altered metabolism of histamine Diagnosis causing a disproportionate increase of Nt-methylhistamine and Nt-methylimidazoleacetic acid in urine. In addiIf mastocytosis is suspected on clinical grounds, the evaluation should include clinical and histological exam-tion to being a reliable way of assessing the extent of systemic involvement, measurement of these metabolites ination of skin, complete blood count with differential, 24-hour urine collection for measurement of mediators periodically can be used to monitor disease activity [62,64]. Serum PGD 2 measurement is also plagued by and a bone marrow aspirate and biopsy.…”