+++
SYSTEMIC CORTICOSTEROIDS
++
Systemic corticosteroids are the treatment of choice for some generalized conditions and are discussed in the chapters dealing with specific diagnoses. Some severe widespread dermatologic syndromes, such as erythema multiforme, toxic epidermal necrolysis, and vasculitis, are best treated with systemic steroids only after consultation with a dermatologist. Other disorders, including urticaria, angioedema, Toxicodendron dermatitis (rhus, poison ivy, or poison oak), and other contact or allergic disorders are potential indications for systemic corticosteroids when an extensive area of skin (>20%) is involved. Patients with severe disease can see significant relief with oral corticosteroids within 12 to 24 hours.5 In one study, small bursts of prednisone (40 milligrams daily for 4 days) markedly reduced the pruritus and hastened the clinical improvement of urticaria.4,6 Patients with poison ivy or oak eruptions who require systemic steroids should be treated with oral prednisone (1 milligram/kg body weight) with a slow 2- to 3-week taper to avoid rebound dermatitis. Other contact or allergic dermatitides may benefit from an abbreviated course (4 days) of oral prednisone. However, oral corticosteroids are relatively contraindicated, or must be used with great care, in those with diabetes, hypertension, active peptic ulcer disease, psychiatric disease, and immunodeficiency. Follow-up within 2 to 3 days with the primary care physician or a dermatologist is needed if oral corticosteroids are prescribed to patients with these comorbidities.
+++
TOPICAL CORTICOSTEROIDS
++
Topical corticosteroids are powerful and useful tools in the management of dermatologic disease. Numerous agents are available for use. They differ in concentration, base components, and cost. Familiarity with a single agent in each potency class is sufficient to treat any steroid-responsive skin ailment safely and effectively. Corticosteroid potency or strength (i.e., the anti-inflammatory property) is measured by the agent's ability to induce vasoconstriction. Agents' strengths are rated by vasoconstricting ability on a scale of 1 to 7 group 1 agents are the most powerful corticosteroids, and group 7 medications are the least potent (Table 248-7). In general, ointments are more potent than creams or lotions.
++
+++
Topical Corticosteroid Strength
++
Marked variation in potency is seen across various corticosteroids, whereas much smaller differences in strength are encountered for different concentrations of individual agents. Many corticosteroids are fluorinated. Fluorination greatly increases the potency but also increases the risk of adverse reactions, and fluorinated formulations should not be used in pregnancy.
++
Use of the appropriate-strength topical steroid is strongly encouraged at the start of therapy. Starting with a less powerful agent is not likely to spare the patient from potential adverse effects or to produce adequate control of the disease. Hydrocortisone, perhaps the most frequently used topical corticosteroid in the outpatient setting, is available over the counter in strengths up to 1% and by prescription in strengths to a maximum of 2.5%. Hydrocortisone is safe and may be used on most body surfaces, including the face, genitalia, flexure creases, and intertriginous zones. It also is safe for use in infants and children. For the treatment of diseases involving the palms and soles, hydrocortisone is a poor choice, because the thickened skin does not allow adequate penetration of this relatively low-potency steroid. Corticosteroids of moderate potency, including triamcinolone acetonide and fluocinolone acetonide, are useful in treating severely inflamed skin and the thicker skin of the scalp, trunk, extensor surfaces, palms, and soles. These agents should not be applied to the face or genitals or used in infants because of the risk of skin atrophy. See Table 248-8 for recommendations on the potency of corticosteroid to use in treating various dermatologic diseases. When using agents found in group 6 or 7, consultation with a dermatologist may be advised.
++
++
Different skin surfaces respond differently to topical corticosteroid therapy; this differential response relates to the absorption of the steroid into the deeper tissues. The relatively thin skin surfaces of the face respond very rapidly to the use of group 7 agents, whereas the thicker skin of the palms and soles requires a highly potent steroid. Irritations for which a low-potency agent may provide the same treatment effectiveness as a higher potency agent include those involving raw, inflamed skin (such skin absorbs medication more rapidly and readily); treatment regions with skin surfaces in frequent contact, such as intertriginous areas (the apposition of two skin surfaces produces enhanced absorption of drug, similar to the effect of an occlusive dressing); and areas of skin under tight clothing, such as the diaper area (absorption of the agent is enhanced due to the occlusive effect of the garment). In general, lower potency agents are acceptable in these situations.
+++
Application of Topical Steroids
++
The application of creams, ointments, gels, and lotions is relatively straightforward. The medication is applied in a thin layer and should be massaged daily into the skin, as directed. Washing the skin before corticosteroid application is unnecessary. Advise patients to follow directions closely both early and late in the treatment course. Using extra medication per dose or applying medication more frequently early in the treatment period is not desirable; likewise, reducing the frequency of application or decreasing the amount of medication as the disease process responds to therapy can cause relapse. Optimal application regimens have not been determined for topical corticosteroids in most dermatologic syndromes. The more potent agents are best applied two to three times daily for 1 to 2 weeks followed by a drug-free week; additional therapy may be required as determined by the disease and by the particular patient's response to the initial therapy. Agents from the less potent steroid groups may be applied three times daily for 2 to 4 weeks followed by a 7-day steroid-free period.
+++
Prescribing the Correct Amount of Topical Steroid
++
Determining the correct amount of topical steroid to prescribe is at times difficult. The burn rule of nines may be used to estimate the amount of topical corticosteroid to prescribe. Calculate the percentage of body surface area requiring therapy and then multiply the percentage by a correction factor of 30. This calculation provides the amount of topical corticosteroid in grams for a single application. Next, determine the number of administrations required in the treatment course. For example, a three-times-daily regimen for a duration of 10 days requires 30 applications. The number of applications is multiplied by the grams required for a single dose to yield the total amount to be prescribed (Table 248-9). In general, 9 grams of topical steroid cover 9% of the body surface area for 1 day with a thrice-daily application. See Table 248-10 for a description of the amount of topical corticosteroid to be dispensed relative to the coverage area and duration of therapy.
++
++
++
Tachyphylaxis refers to the decrease in responsiveness to a drug as a result of enzyme-mediated events. The term is used in relation to topical corticosteroids to describe the early development of tolerance to vasoconstricting ability. In general, vasoconstriction has been demonstrated to decrease progressively over time after a topical steroid has been applied. Such reductions in strength due to tolerance are encountered as soon as 4 days into the treatment course in all potency groups but are thought to be more important for corticosteroids in groups 1 and 2. A reasonable strategy to counter the development of tachyphylaxis is the use of interrupted application schedules. An interrupted treatment course might include an initial three-times-daily application for 2 weeks, followed by 1 week without use of the drug, and then a repeat of the cycle.
++
Antihistamines (histamine-1 antagonists) are useful to control pruritus. These agents include the first-generation antihistamines such as diphenhydramine and hydroxyzine. These histamine-1 antagonists may be used PO, IM, or IV. The second-generation antihistamine agents, including astemizole, cetirizine, fexofenadine, and loratadine, are newer agents that may be used in certain circumstances. In general, the newer antihistamines offer the advantages of reduced dosing frequency and less sedative effect, but they are more costly. Comparisons of these new medications with hydroxyzine are generally favorable, but differences are not dramatic; comparisons of the various second-generation agents do not demonstrate significant differences among them.7,8 Increasing the dosage of these antihistamine medications above their recommended dosages may increase the sedative effect but does not provide greater reduction in itching.9 The use of topical antihistamine preparations is discouraged, because these agents are readily absorbed and dosing is difficult to predict. Accidental overdosage may result in patients who aggressively apply the preparation or are also using similar oral agents. See Table 248-11 for suggested dosing, administration schedules, and routes of therapy for these antihistamines. Histamine-2 antagonists (ranitidine or famotidine) also have demonstrated some benefit in patients with an allergy-mediated event, in particular urticaria, and therefore are recommended in combination with histamine-1 antagonists in the more severe allergic reactions.10,11
++
++
Numerous other antipruritic therapies are recommended, including Domeboro solution (aluminum sulfate diluted 1:10 with water) soaks and oatmeal baths.
++
Topical antibacterial agents are used primarily as adjuncts to wound dressing and are rarely useful as primary therapy for superficial bacterial infections of the skin. The exception to this statement is topical mupirocin, which is as effective as oral antimicrobial agents in the management of impetigo. For wound dressing, the agents commonly used include polymyxin B, bacitracin, neomycin, and silver sulfadiazine. Do not use silver sulfadiazine on the face because it will stain. When reapplying silver sulfadiazine, thoroughly wipe off the prior medication before applying a new dose to avoid silver staining of the skin. Benefits of topical antibacterial agents include reduced adherence of bandaging material to the wound, reduced coagulum, and decreased bacterial colonization. The impact on the rate of wound healing and the prevention of wound infection is less well characterized. Another application of topical antibacterial agents is in the treatment of aphthous stomatitis, for which oral tetracycline rinses are used.
++
Other disorders treated with topical agents include Candida infections, dermatophyte infections, herpes simplex, and lice infestations and scabies. Diagnostic features and specific treatment are discussed in other chapters by the specific diagnosis.
+++
NONANTIMICROBIAL TOPICAL AGENTS
++
In general, the maxim "If it's dry, wet it, and if it's wet, dry it" applies to the initial treatment of many rashes. Water, protein, and lipid losses characterize dry skin diseases. Emollient creams and lotions restore water and lipids to the epidermis, hasten the healing process, and reduce pruritus and pain. Emollients are moisturizers that reduce skin dryness and decrease skin friction and the sensation of tightness. In patients with chronic drying dermatitides, ointments are best, particularly in the winter months. In warm climates, less viscous, less oily preparations, such as a cream, are better tolerated. Open wet dressings using tap water or normal saline not only reduce discomfort due to the drying but also cleanse the skin by painlessly loosening crusts and exudates. The various wet cutaneous syndromes involve similar protein and lipid losses due to excessive flow of transudative or exudative fluid from the diseased skin with leaching of the complex macromolecules of the epithelial cells. Drying agents retard this flow of fluid and associated biologic materials from the body, thus assisting in the curative process.
+++
Topical Agent Medication Base (Vehicle)
++
The vehicle, or medication base, is the substance in which the active ingredient is dispersed. The base determines the rate at which the active ingredient is absorbed through the skin. Components of some bases may cause irritation or allergy.
++
Creams, a mixture of oils, water, and preservative, are white and greasy in texture. Creams are the most versatile vehicle and can be applied to any body surface area. They are particularly useful in the intertriginous areas. Creams are best used for acute therapy only; chronic application may cause excessive drying. Some patients are allergic to the preservatives in creams; in these patients, consider switching to an ointment preparation of the medication.
++
Ointments are composed of greases such as petroleum jelly and are free of preservative. Little water is added to this vehicle. Ointments are translucent and, when applied to the skin, remain greasy. This greasy consistency lubricates particularly dry lesions. In general, ointment vehicles allow deeper tissue penetration compared with cream bases. Ointments also are occlusive, providing very thorough coverage with deep tissue penetration and allowing little movement in moisture and other material into and out of the skin. Acute exudative syndromes and intertriginous areas of the body should not be treated with topical steroids formulated using an ointment vehicle.
++
Gels are greaseless mixtures of propylene glycol and water and at times contain alcohol. Gels have a translucent appearance and are described as "sticky." Alcohol-containing gels are best for acute exudative lesions, such as poison ivy dermatitis, whereas alcohol-free combinations should be used for dry, scaling conditions. In denuded areas, the alcohol component may cause discomfort. Gels are sometimes preferred for the scalp, because they do not alter the hair style and are cosmetically tolerable.
++
Solutions or lotions may contain water or alcohols in addition to other agents. They are clear or milky in appearance and are most useful for the scalp and other dense hair-bearing areas because they leave no significant residue on the hair. In denuded areas, the alcohol component may cause discomfort.
++
Some topical steroids are available as foams. Clobetasol (a very potent topical steroid) is safe and effective as a foam.12 It is important to note that the absorption rate of clobetasol is greater for the foam vehicle formulation than for the topical solution.13
+++
Topical Agent Toxicity
++
Topical agents with certain active ingredients must be used with caution. These ingredients are often very effective, but the delivery is uncontrolled. Although the patient can control the amount and frequency of application, the actual amount of systemic absorption is not easily managed. For instance, certain agents are well absorbed through normal skin and mucous membranes, whereas other medications are absorbed only through irritated skin or mucosa. Topical formulations containing agents absorbed through irritated skin include the Lidoderm patch (containing lidocaine), Caladryl lotion (containing pramoxine, a local anesthetic), Bengay (containing methyl salicylate), and Icy Hot (containing menthol and methyl salicylate). Reports of significant toxicity, including death, have been reported with these and similar agents when excessively applied topically.