The skin is composed of the epidermis, an epithelial layer of ectodermal origin, and the dermis, a layer of connective tissue of mesodermal origin. See generally Fitzpatrick (1999) Dermatology in General Medicine, 5th ed., McGraw Hill. The junction of dermis and epidermis is mostly irregular, and projections of the dermis, known as papillae, interdigitate with evaginations of the epidermis known as epidermal ridges.
The epidermis consists mainly of a stratified keratinized epithelium populated primarily by keratinocytes, which are keratinizing epidermal cells. See id. The epidermis also harbors a number of other cell populations such as melanocytes, Langerhans cells, Merkel cells, and other cellular migrants. From the dermis outward, the epidermis consists of five layers of keratinocytes known as the stratum basale (stratum germinativum), stratum spinosum, stratum granulosum, stratum lucidum and stratum corneum.
The dermis is composed of the connective tissue that supports the epidermis and binds it to the subjacent layer, known as subcutaneous tissue or hypodermis. See id. The dermis has a rich network of blood and lymph vessels. The dermis contains vascular networks situated in parallel to the skin surface at various levels and connected by vertical communicating vessels. The dermis contains two layers with rather indistinct boundaries: the outermost papillary layer and the deeper reticular layer. The papillary layer is composed of a number of different cell types, including loose connective tissue cells, fibroblasts and other connective tissue cells, as well as mast cells and macrophages. Extravasated leukocytes are also detected in the papillary layer. The reticular layer is thicker than the papillary layer and is composed of irregular dense connective tissue (mainly type I collagen).
Many pathologic reactions of the skin involve a combination of epidermal and dermal components. See id. However, frequently one component is more predominantly involved in a given pathological reaction over the other, thus leading to certain clinical diagnoses. See id. For example, a hyperplastic epidermis is characteristic of psoriatic plaques. Examples of pathologic reactions involving superficial skin layers include vesicular dermitis (eczema), contact dermatitis, psoriasis, interface dermatitis, erythema multiforme, lupus erythematosus, lichen planus and dermatitis herpetiformis. Examples of pathologic reactions involving the dermis include acute febrile neutrophilic dermatosis (Sweet's Syndrome), erythema elevatum diutinum, cutaneous eosinophilic disease, granuloma, malignant atrophic papulosis, dermal neoplasm, dermal pseudoneoplasm, dermal hyperplasia, dermal vascular anomaly, Kaposi's sarcoma, anetoderma and atrophic disorder of the skin.
Skin disorders, such as psoriasis, eczema, and lichen planus, are known to affect one to two percent of the U.S. population, with as many as 150,000–260,000 new cases occurring annually (“Research Needs in 11 Major Areas in Dermatology” I. Psoriasis. J. Invest. Dermatol. 73:402–13, 1979). Presently known therapies for the above mentioned skin diseases are limited. Steroids or cyclosporin A are commonly used in the treatment of psoriasis, lichen planus, urticaria, atopic dermatitis, UV damage, pyoderma gangrenosum, vitiligo, ocular cicatricial pemphigoid, alopecia areata, allergic and irritant contact dermatitis and cutaneous T cell lymphoma. In addition, for some of these skin conditions, various therapies include retinoids, PUVA, nitrogen mustard, interferon, chemotherapy, methotrexate, light therapy (e.g., UV light and PUVA), antibiotics and antihistamines. See id. UV light therapies, both UVA and UVB therapy, expose the skin to UV radiation between 320–400 nm (UVA radiation) and 290–320 nm (UVB radiation). PUVA therapy is a form of photochemotherapy that involves repeated topical application of psoralen or a psoralen-based compound to an affected region of skin, followed by exposure of that region to UVA radiation. Another method used to treat proliferative skin diseases, particularly psoriasis and mycosis fungoides, is photodynamic therapy (PDT).
Side effects to these therapies are known. Most commonly encountered drawbacks for cyclosporin A include toxicity due to immunosuppression and renal and neural toxicity. Steroids have well known side effects including induction of Cushing Syndrome. Side effects of certain of the other aforementioned therapies include skin cancer, bone marrow and constitutional toxicities, ligament calcification, liver fibrosis and other disorders. With respect to light therapy, prolonged treatment of skin diseases using these types of therapies can result in significant acute and chronic adverse effects including erythema, pruritus, skin cancer, and chronic light-induced damage of the skin (Stem et al. (1979) N.E. J. of Med. 300:809–812).
Accordingly, there exists a need for improved therapeutic modalities for preventing and treating skin disorders.