Elevated urinary histamine in the hyperimmunoglobulin E and recurrent infection (Job's) syndrome: Association with eczematoid dermatitis and not with infection

Abstract

To test the hypothesis that IgE-mediated release of histamine may be, in part, responsible for the abnormal inflammatory response observed in the hyperimmunoglobulin E (HIE) and recurrent infection syndrome, urine and plasma histamine levels were measured. Twenty-four-hour urinary histamine concentrations from 15 patients with HIE (23.7 ± 6.9 μg/24 hr) were significantly elevated ( p < 0.001) compared to a large historical control population (10.5 ± 0.7 μg/24 hr; n = 97). However, urinary histamine levels in HIE were much less abnormal ( p < 0.01) than in five patients with biopsy-proven systemic mastocytosis (159 ± 62 μg/24 hr) and were not significantly elevated when levels were compared to 13 concurrently studied normal subjects (10.1 ±1.7 μg/24 hr) and nine patients with chronic granulomatous disease (8.1 ± 1.2 μg/24 hr). Overall, there was no clear relationship between urine histamine values and the presence of infection as well as no significant correlation between urine histamine and total IgE or anti- Staphylococcus aureus IgE. However, urine histamine levels in a subgroup of six patients with HIE with chronic eczematoid dermatitis (42.4 ± 12.5 μg/24 hr) were elevated compared with values from the historical control subjects ( p < 0.001), the concurrent control subjects ( p < 0.01), the patients with chronic granulomatous disease ( p < 0.01), and five patients with HIE who did not have skin manifestations (4.6 ±1.1 μg/24 hr; p < 0.05). In related studies, plasma histamine levels were normal (<500 pg/ml) in 19 samples from eight patients with HIE. Thus, histamine is moderately increased in the urine of patients with HIE and is not increased in the plasma. Elevated urine histamine excretion in HIE appears to be related to the presence of eczematoid dermatitis and not to the presence of infection. Therefore, it appears unlikely that abnormal histamine release plays an important role in the pathophysiology of recurrent infections in patients with HIE.