Book Section XIV - Dermatology

The skin has many essential functions, including protection, thermoregulation, immuneresponsiveness, biochemical synthesis, sensory detection, and social and sexual communication.Therapy to correct dysfunction in any of these activities may be delivered topically, systemically,intralesionally, or through ultraviolet radiation.
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Book Section XIV - DermatologySection XIV. DermatologyOverviewThe skin has many essential functions, including protection, thermoregulation, immuneresponsiveness, biochemical synthesis, sensory detection, and social and sexual communication.Therapy to correct dysfunction in any of these activities may be delivered topically, systemically,intralesionally, or through ultraviolet radiation.Topical therapy is a convenient method of treatment, but its efficacy depends on understanding thebarrier function of the skin, primarily within the stratum corneum. Corticosteroids and retinoids areimportant systemic and topical therapeutic agents for skin disease. Oral steroids are employed inhigh doses to treat very serious cutaneous eruptions, and, fortunately, structural modification of thehydrocortisone molecule has produced compounds of increased potency that now can be usedtopically to treat many dermatological diseases. Potent and efficacious retinoids for treatment ofacne and psoriasis are administered orally, and modification of these molecules has resulted intopical agents that are being explored for their anticarcinogenic and antiaging effects. Oralantimalarials, chemotherapeutic agents, immunosuppressive agents, and antihistamines frequentlyare used for treatment of dermatological diseases. It is interesting that controlled ultraviolet (UV)radiation therapy is a frequent mode of treatment for psoriasis, pruritus, and atopic dermatitis,although UV radiation is itself responsible for the production of cutaneous cancers. However, theprophylactic use of sunscreens may reduce or prevent premalignant and malignant skin lesionsinduced by UV light, so their use is highly recommended. Major advances in the development anduse of antifungal agents, antiviral agents, and antibacterial agents for skin diseases have clearlyimproved treatment options. Vitamin D analogs, retinoids, and anthralin are some of the topicalagents used for psoriasis.Much of this chapter is organized according to specific dermatological disorders and drugs used intheir treatment. Separate sections are devoted to glucocorticoids and retinoids because of their broadapplications in dermatology. Agents with narrower spectra of uses are discussed under individualdermatological disorders.Dermatological Pharmacology: IntroductionHistory of DermatologyThe origins of dermatological pharmacology can be found in early Middle Eastern cultures. EarlyEgyptians recorded medical knowledge on special papyri, where mentions of alopecia and itstreatment—consisting of equal parts of the fat of a lion, hippopotamus, crocodile, goose, snake, andibex—are made. Indians used arsenic in the treatment of leprosy and a mixture of mercury andsulfur to treat pediculosis. A paste containing iron sulfate, bile, copper sulfate, sulfuret of arsenic,and antimony was used for pruritus of the scrotum. The Greeks under Hippocrates and the Romansunder Celsus made many other contributions to the field of dermatology (King, 1927).As late as the end of the nineteenth century, dermatological therapy was still archaic by todaysstandards. At the first World Congress of Dermatology in Paris in 1889, one of the favoritetreatments of tinea capitis was dermabrasion with sandpaper followed by application of a solutionof bichloride of mercury. Treatment of syphilis was thought to be best deferred until the secondarystage, at which time application of a 50% mercurous oleate ointment was recommended (Shelleyand Shelley, 1992).The dermatological pharmacopeia has grown rapidly in the past century, as our understanding ofdisease processes has improved. We have shifted our paradigm from the traditional axiom, whichrelied heavily on the physical characteristics of medications for their effect, to one in whichchemical properties hold an equally important role. In the past, dermatological therapy consistedmainly of symptom relief. With advances in technology and knowledge, medications that targetspecific disease processes now are available.The Structure and Function of SkinThe skin has many diverse functions, including protection, thermal regulation, sensory perception,and immune responses. The skin, in a strict sense, consists of the epidermis and its underlyingdermis. However, one usually includes the soft tissue underlying the dermis in a discussion of theskin because of its close apposition to and tendency to react as a unit with the overlying skin.The top layer of the skin is the epidermis. It consists of keratinocytes, melanocytes (pigment),Langerhans cells (antigen presentation), and Merkel cells (sensory). Keratinocytes, the proliferativeportion of the epidermis, contain keratins, which provide internal structure. Each layer of theepidermis expresses different keratins, and keratins often are used as keratinocyte differentiationmarkers. Abnormal keratin expression is a feature of many skin diseases including psoriasis andsome ichthyotic disorders. As keratinocytes mature and differentiate, they become larger and flatterand eventually lose their nuclei. The terminal point of keratinocyte differentiation is the formationof the stratum corneum.Formation of the stratum corneum is arguably the most important function of the epidermis. Thestratum corneum, or horny layer, protects the skin against water loss, prevents the absorption ofnoxious agents, and can be thought of as consisting of bricks and mortar. Corneocytes form thebricks, and barrier lipids form the mortar. Corneocytes are formed by proteins found inkeratinocytes and are located in the upper layers of the epidermis.Granular cells, which are immediately below the stratum corneum, contain basophilic structurescalled keratohyalin granules. These granules contain an inactive precursor protein calledprofilaggrin. Dephosphorylation and proteolysis of profilaggrin to filaggrin occurs as granular cellsmove into t ...