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The dermis is a connective tissue layer sandwiched between the epidermis and subcutaneous tissue. The dermis is a fibrous structure composed of collagen, elastic tissue, and other extracellular components that include vasculature, nerve endings, hair follicles, and glands. The role of the dermis is to support and protect the skin and deeper layers, assist in thermoregulation, and aid in sensation. Fibroblasts are the primary cells within the dermis, but histiocytes, mast cells, and adipocytes also play important roles in maintaining the normal structure and function of the dermis (see Image. Illustration of Cells of the Epidermis).

There are numerous diseases that affect the skin. The following discussion describes some common and uncommon diseases that affect the dermis. This discussion is not all-inclusive but demonstrates the importance of understanding the normal structure and function of the genetic diseases that can affect dermal structure and function. Ehlers-Danlos syndrome is a group of genetic connective tissue disorders caused by various mutations in collagen. The mutations in dermal collagen result in skin hypermobility and fragility. Osteogenesis imperfecta is a genetic disorder of type I collagen, causing decreased dermal collagen and impaired skin elasticity.[18] Marfan syndrome is another genetic condition caused by a defect in the FBN1 gene encoding the fibrillin-1 protein. While skin complaints are not required for diagnosis, patients are prone to the development of striae distensae (stretch marks) due to rapid growth phases in adolescence.[19] These 3 genetic disorders, along with other inherited diseases, may rarely cause reactive elastosis perforans serpingosa, in which transepithelial elimination of elastic fibers manifests clinically as papules in an annular or serpiginous pattern.[20]

There are numerous diseases that affect the skin. The following discussion describes some common and uncommon diseases that affect the dermis. This discussion is not all-inclusive but demonstrates the importance of understanding the normal structure and function of the genetic diseases that can affect dermal structure and function. Ehlers-Danlos syndrome is a group of genetic connective tissue disorders caused by various mutations in collagen. The mutations in dermal collagen result in skin hypermobility and fragility. Osteogenesis imperfecta is a genetic disorder of type I collagen, causing decreased dermal collagen and impaired skin elasticity.[18] Marfan syndrome is another genetic condition caused by a defect in the FBN1 gene encoding the fibrillin-1 protein. While skin complaints are not required for diagnosis, patients are prone to the development of striae distensae (stretch marks) due to rapid growth phases in adolescence.[19] These 3 genetic disorders, along with other inherited diseases, may rarely cause reactive elastosis perforans serpingosa, in which transepithelial elimination of elastic fibers manifests clinically as papules in an annular or serpiginous pattern.[20] Cushing syndrome, chronic glucocorticoid use, and pregnancy are other conditions causing striae distensae. Glucocorticoids inhibit fibroblasts, thus disrupting the synthesis of collagen and ECM material. Histology of striae distensae reveals flattening of the epidermis with loss of rete ridges and changes in the architecture of collagen bundles coupled with elastin degeneration throughout the dermis.[21] The overactivity of fibroblasts has been implicated in many skin-related diseases. Myofibroblasts, expressing alpha-smooth muscle actin (a-SMA), have been implicated in both hypertrophic scars and keloids.[22][23] A careful histopathological examination is required to differentiate among keloids, hypertrophic scars, dermatofibromas, dermatofibrosarcoma protuberans, and scleroderma due to similar histopathologic findings.[24] Lichen sclerosis is an inflammatory disorder involving abnormal fibroblast function in the papillary dermis, causing fibrosis of the superficial dermis and epidermis.[25] Acanthosis nigricans results from increased growth factor receptor signaling causing proliferation of epidermal keratinocytes and dermal fibroblasts, leading to hyperkeratosis and papillomatosis ("peaks and valleys") on histopathology.[26][27] Researchers have also observed persistent activation of fibroblasts in the dermis in morphea and nephrogenic systemic fibrosis.[28]

Cushing syndrome, chronic glucocorticoid use, and pregnancy are other conditions causing striae distensae. Glucocorticoids inhibit fibroblasts, thus disrupting the synthesis of collagen and ECM material. Histology of striae distensae reveals flattening of the epidermis with loss of rete ridges and changes in the architecture of collagen bundles coupled with elastin degeneration throughout the dermis.[21] The overactivity of fibroblasts has been implicated in many skin-related diseases. Myofibroblasts, expressing alpha-smooth muscle actin (a-SMA), have been implicated in both hypertrophic scars and keloids.[22][23] A careful histopathological examination is required to differentiate among keloids, hypertrophic scars, dermatofibromas, dermatofibrosarcoma protuberans, and scleroderma due to similar histopathologic findings.[24] Lichen sclerosis is an inflammatory disorder involving abnormal fibroblast function in the papillary dermis, causing fibrosis of the superficial dermis and epidermis.[25] Acanthosis nigricans results from increased growth factor receptor signaling causing proliferation of epidermal keratinocytes and dermal fibroblasts, leading to hyperkeratosis and papillomatosis ("peaks and valleys") on histopathology.[26][27] Researchers have also observed persistent activation of fibroblasts in the dermis in morphea and nephrogenic systemic fibrosis.[28] Aging and chronic sun exposure can weaken the dermis. Solar elastosis is due to chronic ultraviolet (UV) radiation exposure, resulting in damage to elastic fibers. Histology reveals basophilic degeneration of elastic fibers in the dermis.[29] The reduction of connective tissue in aging, usually with concomitant UV damage, causes actinic purpura (i.e., senile purpura), where the dermis cannot support its vasculature. As a result, minor trauma can lead to extravasation of blood.[30] Similar manifestations may be seen in chronic glucocorticoid users. Glomus tumors can also occur within the dermis and deeper tissues, especially within the digits and palms where glomus bodies are concentrated.[31]

Aging and chronic sun exposure can weaken the dermis. Solar elastosis is due to chronic ultraviolet (UV) radiation exposure, resulting in damage to elastic fibers. Histology reveals basophilic degeneration of elastic fibers in the dermis.[29] The reduction of connective tissue in aging, usually with concomitant UV damage, causes actinic purpura (i.e., senile purpura), where the dermis cannot support its vasculature. As a result, minor trauma can lead to extravasation of blood.[30] Similar manifestations may be seen in chronic glucocorticoid users. Glomus tumors can also occur within the dermis and deeper tissues, especially within the digits and palms where glomus bodies are concentrated.[31] Urticaria is an inflammatory dermatosis characterized by vascular hyperpermeability, causing superficial dermal edema with resultant lymphatic dilation. The pathogenesis of urticaria often involves degranulation of mast cells and immunoglobulin E-dependent pathways; however, this is not true for all cases.[32] Mastocytosis describes a spectrum of rare diseases involving an increase in mast cells within the skin and other organs. Urticaria pigmentosa is the most common cutaneous form of mastocytosis and predominately occurs in childhood.[33] Granulomatous diseases such as sarcoidosis, granuloma annulare, necrobiosis lipoidica, and mycobacterial infections (tuberculosis, leprosy) involve histiocytes within the dermis. Mycobacterium leprae infects Schwann cells of peripheral nerves, leading to diminished or absent cutaneous sensation in leprosy.[34] Lymphocytic infiltration of the dermis causes diseases such as polymorphous light eruption, a common photosensitive dermatosis.[35] Cutaneous manifestations of hematologic malignancy, such as leukemia cutis, also involve leukocytic infiltration into the skin layers. Sweet syndrome is a rare condition associated with neutrophilia and neutrophilic infiltration into the reticular dermis.[36] Other disorders involve the deposition of foreign material within the dermis, such as cholesterol in xanthelasma and protein fibrils in amyloidosis.[37] Burns and ulcers are important to consider as the depth of burn or wound involvement affects patient diagnosis and management. Partial-thickness burns, also known as second-degree burns, destroy the epidermis and extend into the dermis.[38] Similarly, stage II pressure ulcers, as described by the NPUAP, expose the dermis.[39]