Ground substance (extrafibrillar matrix) is finely granular extracellular material that enmeshes fibrillar and cellular components of the body, including those of the dermis, binds water, and provides hydration to the skin. The ground substance of normal skin consists mainly of water, electrolytes, plasma proteins, and mucopolysaccharides. A mucopolysaccharide consists of a long-chain, aminated polysaccharide (glycosaminoglycan) linked covalently to a polypeptide. The terms mucopolysaccharide, mucosubstance, mucin, and proteoglycan are used interchangeably to refer to the entire polysaccharide-polypeptide complex. Fibrocytes produce glycosaminoglycans that, in the dermis, are made up mostly of hyaluronic acid and dermatan sulfate in conjunction with smaller amounts of chondroitin 6-sulfate, heparan sulfate, and heparin.

Although they constitute only 0.2% of the dry weight of the skin, glycosaminoglycans account for most of the volume of the dermis because they retain water in amounts up to 1,000 times their own volume. After loss of water-laden glycosaminoglycans during processing of sections in routine fashion and staining by hematoxylin and eosin, ground substance, when viewed through a conventional microscope, is not visualizable, only empty spaces being apparent between bundles of collagen. Specialized stains, such as colloidal iron and Alcian blue, are required to demonstrate the presence, albeit in scant amount, of acid mucopolysaccharides in the normal dermis, they being observable best in the papilla of follicles in anagen and around eccrine glands. At those two sites, acid mucopolysaccharides often are recognizable in routine sections as basophilic, finely granular, stringy material.

Mucin is increased strikingly in the reticular dermis of several inflammatory diseases, chief among them being lupus erythematosus and dermatomyositis diffusely, and granuloma annulare focally.