More than 70% of the dry weight of the normal dermis consists of collagen (Fig. 1.79). The major collagens are Type I and Type III. Type I collagen has a molecular mass of about 290 KDa and accounts for approximately 80% of the total amount of collagen in the dermis. Type I collagen is arranged in a dense orthogonal meshwork of bundles in the reticular dermis. Type III collagen makes up approximately 10% of dermal collagen, it being called also fetal collagen because it is noted first in embryonic dermis where it serves as a framework on which Type I collagen subsequently is synthesized. Collagen of Type III appears principally as loosely arranged argyrophilic fibers in the adventitial dermis, that being a continuum formed by the papillary and periadnexal dermis. Although Type III collagen, known, too, as reticulin, is found in the adventitial dermis especially, it is present throughout the entire dermis, being associated closely with Type I collagen. Together, Types I and III collagen form the extracellular fibers that are responsible largely for the tensile strength of the dermis. Mutations in genes in Types I and III collagen may result in abnormalities of connective tissue both in the skin and in joints, as well as in other tissues, in different expressions of Ehlers-Danlos syndrome, and in fragility of bone in osteogenesis imperfecta.

Figure 1.79

Collagen fibrils cut longitudinally have a structure distinctly different from that of the elastic fibril pictured, the latter consisting of noncollagenous microfibrils embedded in homogenous elastin. (x55,000) (Courtesy of Richard Wood, Ph.D.)

Type II collagen is found in cartilage. Type IV collagen is a constituent of basement membrane and is located especially in the lamina densa. The alpha 5 chain of type IV collagen has been shown to be a target of circulating IgG autoantibodies in a novel autoimmune disease characterized by sudden onset of extensive subepidermal bullae in company with lesions of mucosa and by nephropathy. Type V collagen accounts for less than 5% of all collagen in the dermis. Mutations in genes of Type V collagen have been discovered in patients with autosomal dominant forms (Type I and Type II) of Ehlers-Danlos syndrome. Type VI collagen may be copious in a variety of tissues, including skin where it is assembled into relatively thin microfibrils that form a network which acts as an anchor for stabilizing the assembly of broad collagen fibers, as well as serving as a basement membrane. Mutations in Type VI collagen may result in different manifestations of congenital muscular dystrophy, with no distinctive phenotype in the skin but with limited joint mobility.

Type VII collagen is produced mostly by keratocytes, from which it is transported across the basement membrane at the dermoepithelial junction to its final destination, that is, anchoring fibrils in the papillary dermis. In the papillary dermis, Type VII collagen interacts with anchoring plaques at one end and with Type IV collagen and/or laminin 5 components of the basement membrane at the dermoepidermal junction at the other, thereby stabilizing the attachment of the basement membrane to the dermis. Alteration in the expression, structure, or molecular interactions of Type VII collagen with other components of the basement membrane may cause the skin to be fragile. Absence of and/or abnormalities in Type VII collagen and anchoring fibrils have been demonstrated in the dominant form of epidermolysis bullosa, and in some cases of the severe recessive dystrophic form, a group of heritable bullous diseases typified by blistering of the skin in response to minor trauma.

Type XIII collagen is transmembrane protein, an expression of which has been detected in normal skin and in cultured keratocytes. It is localized to the dermoepidermal junction and to the periphery of keratocytes that reside at all layers of the epidermis, thereby identifying Type XIII collagen as a cell adhesion molecule that may play a part in enabling keratocytes to adhere to one another. Type XVI collagen, a member of the fibril-associated collagens with interrupted triple helices, is produced not only by fibrocytes, but by keratocytes. It is a component of the extracellular matrix and is confined to a narrow zone in the papillary dermis near the basement membrane, in close proximity to Type VII collagen and to collagen of blood vessels. Type XVII collagen is a transmembrane protein characterized by alternating segments, collagenous and noncollagenous. It was recognized initially as the 180 KDa bullous pemphigoid antigen 2, a constituent of anchoring filaments at the basement membrane, and now is known to be one of the targets of circulating IgG autoantibodies in the serum of some patients with bullous pemphigoid, herpes gestationis, linear IgA dermatosis, and cicatricial pemphigoid.

Fibroplasia, a process in which fibrocytes, increased in number during the active phase of it, manufacture collagen organized abnormally, is an expected finding in some kinds of inflammatory diseases of the skin, e.g., those that occur secondary to trauma, such as scars, keloids, and dermatofibromas; those marked by extensive suppuration and subsequent degeneration of collagen, such as ruptured epidermal (infundibular) and follicular (isthmus-catagen) cysts, deep fungal infections and atypical mycobacterial infections, and pyoderma gangrenosum; and those typified by long-standing lichenoid infiltrates of lymphocytes, such as lichen planus, disseminated superficial actinic porokeratosis, and some examples of the lichenoid purpura of Gougerot and Blum (and the neoplastic process, mycosis fungoides, during the patch/plaque stage) and of bandlike infiltrates of plasma cells, as in acrodermatitis chronica atrophicans.