Ultrastructure and composition of connective tissue in hyalinosis cutis et mucosae skin

Skin biopsies from a patient with hyalinosis cutis et mucosae (HCM) were studied by routine histology, electron microscopy, biochemical extractions, and immunofluorescence for extracellular matrix proteins. The upper dermis consisted of large hyaline regions mainly composed of noncollagenous proteins. A portion of this material was solubilized by reduction in 8 M urea. Anti-sera against these proteins revealed multiple antigens most of which were also detectable in normal skin. The hyaline regions showed a reduced content of collagens, particularly of thick fibrils and of fibronectin. The basal lamina around capillaries and at the dermal-epidermal junction appeared as multiple, concentric layers of amorphous laminae intercalated with thin collagen fibrils. They consisted of collagens type III and IV and of laminin as shown by immunofluorescence. Antibodies could also be raised against laminin of HCM skin which showed strong cross-reactions with authentic mouse laminin. Cultured fibroblasts from the HCM lesion showed increased synthesis of noncollagenous proteins at the expense of newly synthesized collagens. Some but not all of these noncollagenous proteins were also produced by fibroblasts from normal skin. The above data indicate that the hyaline material in HCM originates from the overproduction of noncollagenous proteins, most of which are normal constituents of human skin.