OVERVIEW

many treatments for the skin are topical, meaning they are applied directly to the skin surface.
different formulations of topical treatments are used depending on the site and the type of skin disease.
medicated topical treatments should be applied to the diseased skin only and emollients are applied all over.
systemic therapies are generally used for more severe disease and may need careful monitoring.
biological therapies are delivered by injection or infusion intermittently

Introduction

The treatment of skin disease has evolved dramatically over recent years. Historically, patients were admitted for intensive nursing with extemporaneously prepared combinations of topical steroids, tars, pastes and bandaging. Today however, there is a much greater emphasis on outpatient treatment. Quality control and cost issues have seen a reduction in the number of extemporaneous products available, and there have been exciting new developments in both topical and systemic treatment, particularly with the advent of monoclonal antibodies.

Topical therapy

The skin has the advantage of being readily amenable to treatment with topical therapy. Relatively high concentrations of medication can be applied to the skin safely, with good efficacy and comparatively few side effects. Several factors govern the choice of topical treatment, such as formulation, frequency of application, site and severity of skin disease and patient ability to apply local therapy. Complications tend to be local irritant or allergic reactions. The choice of topical treatment depends on the disease process, pharmaceutical properties of the drug, site of application and cosmesis.

Emollients

Emollients are important in the treatment of dry, scaly and inflammatory skin conditions as they help reduce transepidermal water loss from a damaged epidermal barrier. They soften dry skin by filling in the spaces left by desquamating keratinocytes.

The constituents of an emollient or topical base have significant properties. Lipids, for example, cover the stratum corneum to prevent evaporation of water. White and yellow soft paraffin and liquid paraffin are extracted from crude oil. They are stable, inert hydrocarbons, which form the basis of most commercially available ointments and emollients. Emulsifying agents are used to stabilise emulsions, which are immiscible mixtures of aqueous and oily constituents, and penetration enhancers, such as urea and propylene glycol, may be used to increase penetration of an active component through the skin. Humectants are compounds with a high affinity for water, which are able to draw water into the stratum corneum and have useful emollient properties.

The properties of various formulations of topical therapy are outlined in Table 26.1. Emollients can be applied liberally and regularly to all areas of dry skin.

Table 26.1 Comparison of formulations for topical therapy.

Formulation	Characteristics	Advantages	Disadvantages
Ointments	Oil-based. Provide occlusive film over skin and help retain water. Aid skin hydration and penetration of topical treatment	Tend not require preservatives as lack of water in preparation prevents microbial growth	Greasy and cosmetically less appealing to use
Creams	Emulsions containing water and oil. May be composed of oil in water or water in oil (oily creams). Aid skin hydration, but generally less effectively than ointments	Cosmetically acceptable	Contain preservatives, which may cause sensitisation
Lotions	Watery suspensions, often containing alcohol	Easily spread over a large area. Evaporation of water or alcohol has a drying, cooling effect Cosmetically acceptable Useful for hair-bearing areas, such as the scalp	Contain preservatives and therefore have sensitising potential. Alcohol may cause stinging
Gels	Semisolid emulsion in alcohol base. Useful for suspending insoluble drugs Good absorbent properties	Tend to dry on skin Useful for hair-bearing areas. Cosmetically acceptable especially for use on the face	Relatively high irritant and sensitising potential

Bath emollients and soap substitutes are as important as regular emollients in the treatment of dry skin conditions. Soaps are detergents that irritate the skin by removing intercellular lipids and disrupt the barrier function of the stratum corneum, and should therefore be avoided.

Topical immunomodulatory treatments

Topical corticosteroids

Mode of action

The development of topical corticosteroids in the 1950s revolutionised the treatment of skin disease. Since then, they have been used to treat a wide range of inflammatory dermatoses. The mechanism of action is complex. Steroid diffuses through the stratum corneum, cell membrane and into the cytoplasm of keratinocytes where it binds to the glucocorticoid receptor causing activation. The ligand-bound receptor enters the nuclear compartment and interacts with glucocorticoid response elements (GREs), resulting in the modulation of gene transcription. In addition, the ligand-bound receptor may also inhibit other transcription factors. The overall effect is to suppress inflammatory cytokines, inhibit T-cell activation and reduce cell proliferation.

Classification of topical steroids

Topical corticosteroids are classified according to their potency, which is thought to be related to their glucocorticoid receptor affinity.

Topical steroids are divided into four classes:

Class 1 Super-potent (600 times as potent as hydrocortisone): for example, clobetasone propionate (Dermovate®).
Class 2 Potent (150 times as potent as hydrocortisone): for example, betamethasone valerate (Betnovate®).
Class 3 Moderate (25 times as potent as hydrocortisone): for example, clobetasone butyrate (Eumovate®).
Class 4 Mild—hydrocortisone.

This classification allows determination of the relative strength and therefore the potential side effects of therapy. Generally, the weakest steroid to effectively treat the skin condition should be chosen. Milder steroids should be used on the face and flexural sites. (Table 26.2 provides a detailed outline of topical steroids and their relative potencies).

Table 26.2 Relative potency of topical corticosteroids.

Generic name	Proprietary name	Potency
1% hydrocortisone	Efcortelan®	Mild
1% hydrocortisone acetate and 1% fusidic acid	Fucidin H®	Mild
1% hydrocortisone, 1% nystatin 100 000 units/g and 3% oxytetracycline	Timodine®	Mild
Clobetasone butyrate 0.05%	Eumovate®	Moderate
Alclometasone dipropionate 0.05%	Modrasone®	Moderate
Betamethasone valerate 0.1%	Betnovate®	Potent
Mometasone furoate 0.1%	Elocon®	Potent
Diflucortolone valerate 0.1%	Nerisone®	Potent
Betamethasone dipropionate 0.05% and 3% salicylic acid	Diprosalic®	Potent
Betamethasone valerate 0.1% and fusidic acid 3%	Fucibet®	Potent
Clobetasol propionate 0.05%	Dermovate®	Super-potent
Clobetasol propionate 0.05%, neomycin sulphate 0.5% and nystatin 100 000 units/g	Dermovate NN®	Super-potent

Topical corticosteroids should be applied ‘sparingly’. However, this is difficult to define and therefore the fingertip unit (FTU) system was devised. One FTU (a line of ointment from the tip of the finger to the first skin crease) is sufficient steroid to treat a hand-sized (palmar and dorsal surface) area of affected skin. In medical practice, it is common for patients to use insufficient amounts of topical steroids due to the fear of potential complications.

Side effects of topical steroids

Skin atrophy (Figure 26.3)
Telangiectasia
Striae (Figure 26.1)
Ecchymoses
Hirsutism
Folliculitis
Perioral and periorbital dermatitis (Figure 26.2)
Steroid-induced acne/rosacea (Figure 26.3)
Absorption and suppression of the hypothalamic pituitary axis (HPA)

c26f001 — **Figure 26.1** Liberal application of a potent topical steroid resulting in striae formation.

c26f002 — **Figure 26.2** Perioral dermatitis caused by local application of topical steroids.

c26f003 — **Figure 26.3** Potent topical steroid induced atrophy and acne.

Calcineurin inhibitors

Topical tacrolimus and pimecrolimus were originally developed for the treatment of eczema (in patients over the age of 2 years). These agents inhibit calcineurin (a calcium and calmodulin-dependent serine/threonine phosphatase) and suppress T-cell activation. Topical tacrolimus has also been used to treat alopecia areata, oral and genital lichen planus, pyoderma gangrenosum, cutaneous graft versus host disease and vitiligo with varying degrees of success. Pimecrolimus is less potent than topical tacrolimus and is used predominantly in the treatment of eczema in children as a steroid-sparing agent.

Topical antimicrobials

A number of topical antimicrobial preparations are available, some of which are summarised in Table 26.3.

Table 26.3 Topical antimicrobials used in the treatment of superficial infections.

	Preparation	Indications	Complications
Topical antibiotics	Fusidic acid (Fucidin ointment®)	Staphylococcal infections	Resistance
	Mupirocin (Bactroban ointment®)	Gram positive and some gram negative organisms Treatment of nasal staphylococcal carriage	Resistance
	Silver sulfadiazine (Flamazine®)	Pseudomonal infection and some prophylaxis against staphylococcal infection	Minimal absorption and renal impairment when applied to extensive burns
Topical antibiotics used in the treatment of acne	Tetracyclines Erythromycin Clindamycin	Acne May be used in combination with keratolytics such as benzoyl peroxide	Resistance May stain clothing yellow
Topical antifungals	Allylamines Terbinafine cream (Lamasil cream®)	Fungicidal against dermatophyte infections	Ineffective against dermatophyte infections of the nails and scalp
	Imidazoles Clotrimazole (Canesten®) Econazole Ketoconazole Miconazole	Fungistatic Active against Candida and Pityrosporum Maybe used in combination with topical steroids Used in the treatment of intertrigo, pityriasis versicolor and some dermatophyte infections	Concurrent use of topical steroid may mask infection
	Amorolfine (Loceryl lacquer®)	Fungistatic Used in the treatment of onychomycosis Some activity against Scytalidium Synergistic activity with systemic antifungals	Poor cure rates in dermatophyte infections affecting the nail matrix when used as sole therapy
Topical anti-virals	Aciclovir cream (Zovirax®)	Used to treat labial and genital herpes simplex	Needs to be applied as early as possible in the episode for maximum benefit
Anti-parasitic agents	Permethrin	5% cream used in the treatment of scabies and pubic lice. 1% rinse used to treat head lice	Require two treatments 1 week apart
	Malathion	Used in the treatment of scabies, head lice and pubic lice	Alcoholic lotions can irritate skin and can exacerbate eczema Resistance

Miscellaneous topical therapy used in the treatment of psoriasis

These are outlined in Table 26.4.

**Table 26.4** Miscellaneous preparations used in the treatment of psoriasis.

Tags: ABC of Dermatology

Apr 7, 2016 | Posted by admin in Dermatology | Comments Off

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Formulary

OVERVIEW

Introduction