Severe itching for unknown reasons has been reported after administration of hydroxyethylstarch (HES) in haemodilution therapy of humans. After HES treatment, vacuoles in cells of various organs in humans have been shown, predominantly affecting the mononuclear phagocyte system. These vacuoles present indirect evidence for phagocytosis of HES particles. Since phagocytosis is also known to occur in the skin, this organ might represent a target for HES deposition, resulting in subsequent release of mediators responsible for the observed itching. The aim of the present investigation was to study skin biopsies of patients, who had received HES and suffered subsequently from itch. Skin sections were investigated for morphological impairment by means of light and electron microscopy, immunohistochemistry and immunoelectron microscopy using a polyclonal anti-HES antiserum. Storage of HES was demonstrated in the skin of all patients, mainly in dermal macrophages, endothelial cells of blood and lymph vessels, some perineural cells and endoneural macrophages of larger nerve fascicles, some keratinocytes and Langerhans cells. Treatment with antihistaminic agents proved ineffective in these patients; this fits with the observation that morphological signs of histamine release from mast cells were absent. These findings indicate that other mediators from HES-affected cells must be responsible for the development of the itching. Thus, investigation of HES storage may be a useful contribution to the elucidation of release of itch mediators and induction of pruritus.

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Tissue storage of hydroxyethyl starch (HES), a widely used artificial colloid, has been reported. In order to clarify whether storage of HES can be detected in tissues by immunohistochemical methods, use was made of a polyclonal rabbit anti-HES antiserum. Thirteen days after a single intravenous injection of HES rats were sacrificed and liver, spleen, lymph node, lung, kidney and skin were removed. On paraffin sections in all organs the anti-HES antiserum stained mainly cells which could be attributed to the mononuclear phagocyte system, as confirmed by the use of the antimacrophage monoclonal antibody ED 1. The use of a polyclonal anti-HES antiserum may allow analysis of long-term storage and possible side effects in various tissues of man.

Using the highly sensitive ELISA technique for detecting anti-hydroxyethyl starch (HES) antibodies in man sera from 1,056 patients were analyzed. Patients of both sex, who had never had any prior contact with HES, were included in the study. In none of the cases could any titer of HES-reactive antibodies be detected. These data suggest that in man preformed HES-reactive antibodies do not exist or are extremely rare. In any case, unlike dextran-reactive antibodies, they should not have a high clinical importance. The mechanism behind the very rarely observed anaphylactoid reactions after HES application is still unknown.