Dermatologic treatment usually involves the use of topical therapy, which is a disci- pline unto itself. This form of treatment was primarily an art until about 20 years ago.

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4 ^Therapy

Dermatologic treatment usually involves the use of topical therapy, which is a disci- pline unto itself. This form of treatment was primarily an art until about 20 years ago.

Since then science has begun to unravel the biology of the epidermis, making it a more scientific process. Much of topical therapy is simply not written down and it is more com- plicated than the old bromide, “If it’s wet, dry it; if it’s dry, wet it.” This discussion will cover some basic principles of topical therapy, but is by no means exhaustive. As with any form of treatment, there are rules to follow and precautions to take.

This chapter will discuss the following topics:

1. Percutaneous absorption.

2. Vehicles.

3. Occlusion.

4. Topical steroids.

5. Emollients.

6. Enhancers.

7. Other topical agents.

8. Systemic steroid therapy.

9. Intralesional steroid therapy.

10. Antihistamines.

CLINICAL APPLICATION QUESTIONS

An 11-month-old infant presents at your office with an intensely pruritic generalized atopic dermatitis with multiple areas of excoriation and lichenification in some flexor locations. The eruption spares only the diaper area, the palms, and the soles. Most skin regions are dry and fissured.

1. Should you treat this patient with topical steroids, and if so, what type of topical steroids?

2. Should you treat this patient with systemic steroids, and if so, what type of sys- temic steroids?

3. Should you apply occlusive dressings in this patient over the affected areas, and if so, what type of occlusive dressings?

4. Should you treat this patient with an emollient, and if so, why?

5. Is this patient an appropriate candidate for antihistamines, and if so, why?

37

From: Current Clinical Practice: Dermatology Skills for Primary Care: An Illustrated Guide D.J. Trozak, D.J. Tennenhouse, and J.J. Russell © Humana Press, Totowa, NJ

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Percutaneous Absorption

The stratum corneum is the major barrier to any substance applied to the skin surface.

Removing this layer increases permeability by a factor of 10

⁴

. The skin surface shows marked variation in permeability and can be divided into four separate regions (see Fig. 46).

Figure 46: Regions of skin permeability.

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Regions of low permeability will be most resistant to the effects and side effects of topical agents. Those with high permeability will respond more readily to treatment, but are more prone to complications.

Because the epidermis is the major barrier, abraded or damaged skin will be more sus- ceptible to the effects and side effects of topically applied substances. Atopic dermatitis, exfoliative eruptions, and skin that is fissured or ulcerated exhibit enhanced absorption of applied substances because of alterations and breaks in the barrier. Typical plaque psoria- sis has an absorptive capacity similar to normal skin; however, thick scale or crusting will markedly decrease the absorptive capacity.

Other factors that affect penetration include the molecular structure of the active med- ication, the vehicle, occlusion, and additives such as urea and salicylic acid.

A warning regarding topical therapy in infants and children is warranted. Although most studies show similar barrier function in children and adults, children show greater percutaneous absorption of topical agents such as corticosteroids. This is explained by the child’s increased skin-surface-to-weight ratio and the occlusive effect of diapers and plas- tic pants when medication is applied to the diaper area.

All these factors should be considered when prescribing a topical agent.

Vehicles

The delivery of a compound to the stratum corneum is a complex interaction between the vehicle and the active moiety. In general, gel and ointment vehicles are more effective in this regard than are creams and lotions. “Optimized” vehicles have altered this old rule so that some steroid preparations now have cream and ointment bases of equivalent potency. The vehicle also affects treatment by the degree of patient acceptance and, there- fore, compliance.

Gels: Apply easily and disappear without a visible residue. Unfortunately, most have a high propylene glycol content and burn or sting when applied to abraded or intertrigi- nous skin. They are most useful on the scalp and hair-bearing regions of the trunk where the epidermis is thick.

Ointments: Are composed primarily of petrolatum and tend to be simple vehicles.

They have the drawback of leaving a distinct residue that imparts a greasy feel and a shiny appearance. They also discolor clothing worn over the site. Ointments are best used on dry scaling lesions. They seldom burn or sting and restore moisture and flexibility to the sur- face. They are also valuable in patients who are allergic to the more complex cream bases.

Do not use them to treat macerated, moist, or oozing lesions.

Creams: Are the most popular topical vehicles because they feel cool and soothing when applied and disappear shortly after application. Except for the products with opti- mized vehicles, most creams are weaker than their ointment counterparts. They have high patient acceptance and can be used in most locations except dense hairy areas and ear canals, where an unacceptable accumulation of base occurs. Creams with high propylene glycol content will sting when applied to abraded sites.

Lotions: Are liquid preparations that leave a minimal residue. The base may be pre-

dominantly alcohol, propylene glycol, or an oil-in-water emulsion. Alcohol-based lotions

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are dispensed in dropper bottles and are most effective in the scalp, where they leave no residue and do not alter the hair texture or manageability. Because of their drying effect and irritancy, usage is limited. Propylene glycol-based lotions are also used primarily in thick hair-bearing regions and seem to penetrate thick scale more effectively. Unfortu- nately they give the hair a matted, shiny appearance, which makes compliance a problem.

Oil-in-water emulsion bases are soothing and disappear rapidly without visible residue.

They are usually employed in moist macerated sites or on exposed skin such as the face.

They have high patient acceptance.

Foams: Are the newest vehicles available and have been devised to replace older spray products that have been phased out because of their banned propellants. These foam products rapidly melt at skin temperature into a liquid form with minimal residue and are particularly useful in dense hair-bearing areas such as the scalp. Foams appear similar to gel vehicles in their ability to release the active ingredient. Those currently available sting when applied to open or abraded areas, however.

Occlusion

Occlusive therapy with impermeable wraps can greatly enhance the penetration of topical corticoids but is associated with increased side effects and complications. Because of the increased efficacy of topical steroids, occlusive therapy is no longer commonly used. A dermatosis that requires this type of treatment is best referred to a dermatologist.

Topical agents are not innocuous. Be familiar with all the characteristics of the topical agent prescribed.

Topical Steroids

These are available in an extensive array of vehicles and potencies. Side effects, both local and systemic, have been well documented; the incidence increases with potency or with use of an inappropriate compound on an area of high permeability, or usage over large surface areas. For these reasons, topical corticoids should be carefully monitored regarding the quantity used and the total surface area of application. This is particularly true in infants and children, for the reasons cited earlier in this chapter.

There are several questions that should be asked when choosing a topical steroid:

1. How steroid-responsive is the condition to be treated?

2. How permeable is the skin region afflicted; therefore, how susceptible is it to local side effects?

3. What percent of body surface area is involved; hence, what is the risk of systemic effect?

4. What vehicle should be used? This is usually dictated by skin region, condition of the skin surface, and to a lesser degree by patient preference.

5. What is the overall cost of treatment? Sometimes a more expensive product is less

costly due to rapid effect. In other situations, an inexpensive generic may be all

that is needed. The vehicle has a profound effect on these agents and studies have

shown marked variation in biological potency among products with the same con-

centration of active ingredient. All topical steroids are not created equal; the prac-

titioner must be familiar with the activity of the specific product prescribed,

whether it is brand-name or generic.

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Topical corticoids are divided according to potency into seven groups, from the group I “superpotent” products to the weakest group VII preparations. Some of the latter are available over the counter. All practitioners should be conversant with this system and should also be familiar with which products contain a fluo- rinated versus a nonfluorinated active ingredient (see Table 1).

Fluorinated steroids have special side effects when applied to facial skin, genital, and intertriginous regions. Dermatologists try to avoid their use in these areas.

Areas of very high skin permeability include the face and anogenital regions. For such areas, use nonfluorinated group VI or VII products with active ingredients such as des- onide, aclometasone, or higher concentrations of hydrocortisone. Use them with caution.

Twice-daily application is usual.

The scalp, neck, axillae, and flexures of the extremities have high permeability, and group IV through VII preparations are best. Always use the weakest effective product. An exception is on the scalp when there is thick scale present. Then, potent lotions such as clobetasol proprionate or betamethasone diproprionate may be needed.

The skin of the trunk and outer extremities is less permeable. Here group II through group VII steroids are recommended, and group I superpotent products can be used for short periods of time.

Palms, soles, elbows, and knees have low permeability and often require group I super-potents to achieve an adequate effect. Brand-name or generic products containing betamethasone diproprionate, clobetasol proprionate, or diflorasone diacetate in special optimized vehicles are currently the only true group I preparations. Weaker products should be used whenever possible. Application is usually BID except for the palms, where activity and washing during active hours will require more frequent use. On palm and sole lesions with thick scale, enhancers such as urea or salicylic acid may be required.

In order to minimize side effects, become familiar with the pitfalls of these agents and consider these general rules:

1. Use a topical steroid of sufficient potency to control the disease, but aim for the weakest effective preparation.

2. In skin regions of high and very high permeability, use group VI or VII steroids only, and then only with caution.

3. When the disease is controlled, shift to bland lubrication or the weakest corticoid for maintenance. If possible, try to use intermittent therapy with rest periods.

4. With children, exercise caution with all groups of corticoids, especially when used in the diaper area. When possible use 1 to 2.5% hydrocortisone acetate, which, except for instances of gross abuse, has a long safety record.

5. When control of the disease is lost, assess the situation. A complicating infection or side effect of the corticoid may be present.

With use of superpotent corticoids, the following guidelines are recommended:

1. Use daily in short courses of 2 weeks or less and limit total dose to 45 to 50 g/wk.

2. Avoid use in children or in pregnant or lactating patients.

3. Do not use in regions of high or very high skin permeability.

4. After 2 weeks switch to intermittent therapy or to a weaker product.

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Table 1

Potency of Topical Steroids

This listing is not all-inclusive and is based on potency as measured by vasoconstrictor assay. Group I compounds are referred to as “super-potent” products. Temovate and Ultra- vate are considered more potent than the others in group I. The remaining groups are arranged in descending order of potency and products with these groups are biologically and clinically equivalent.

Group Brand / Vehicle Generic Name Conc.%

I Superpotency

a

Temovate cream Clobetasol proprionate 0.05

Temovate ointment Temovate gel Olux foam

Ultravate cream Halobetasol proprionate 0.05

Ultravate ointment

Vanos cream Fluocinonide 0.1

a

Diprolene ointment Betamethasone diproprionate 0.05

a

Psorcon ointment Diflorasone diacetate 0.05

a

Cordran tape Flurandrenolide 4 mg/cm

²

II High potency

a

Aristocort-A cream Triamcinolone acetonide 0.5

Cyclocort ointment Amcinonide 0.1

a

Diprolene AF cream Betamethasone diproprionate 0.05

a

Diprolene gel

a

Diprolene lotion

b

Elocon ointment Mometasone furoate 0.1

Fluocinonide 0.05

(cream, ointment, solution, gel)

Maxiflor ointment Diflorasone diacetate 0.05

Topicort cream Desoximetasone 0.25

Topicort gel 0.05

Topicort ointment 0.25

III High potency

a

Aristocort-A ointment Triamcinolone acetonide 0.1

Cutivate ointment Fluticasone proprionate 0.005

Cyclocort cream Amcinonide 0.1

Cyclocort lotion 0.1

Diprosone cream Betamethasone diproprionate 0.05

Diprosone lotion 0.05

Maxiflor cream Diflorasone diacetate 0.05

Topicort LP cream Desoximetasone 0.05

Betamethasone valerate ointment 0.1 IV Medium potency

Triamcinolone acetonide ointment 0.1

b

Elocon cream Mometasone furoate 0.1

b

Elocon lotion 0.1

Luxiq foam Betamethasone valerate 0.12

b,c

Pandel cream Hydrocortisone buteprate 0.1

Capex shampoo Fluocinolone acetonide 0.01

Continued

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5. With prolonged use consider periodic monitoring of the hypothalamic–pituitary axis.

6. Do not use group I products under occlusion.

7. Maintain careful control of quantities prescribed.

8. Beware of enhanced systemic risks in persons with liver disease, diabetes, glau- coma, or prior tuberculosis.

9. Beware of enhanced systemic toxicity due to interactions in persons concurrently taking sulfonamides and nonsteroidal anti-inflammatory drugs (NSAIDs).

Emollients

The role of emollients in the treatment and maintenance of the epidermal barrier can- not be overemphasized. Proper use of hydrating agents will maintain comfort, improve

Table 1 (Continued)

Group Brand / Vehicle Generic Name Conc.%

V Medium potency

Cutivate cream Fluticasone proprionate 0.05

b

Dermatop cream Prednicarbate 0.1

b

Desonide ointment 0.05

Triamcinolone acetonide lotion, cream 0.1 Triamcinolone acetonide ointment 0.25

b,c

Locoid cream Hydrocortisone butyrate 0.1

b,c

Locoid ointment 0.1

b,c

Locoid solution 0.1

Betamethasone valerate cream 0.1

b,c

Hydrocortisone valerate 0.2

(cream, ointment) VI Low potency

b

Aclovate cream Aclometasone 0.05

b

Aclovate ointment Aclometasone 0.05

b

Desonide cream 0.05

Triamcinolone acetonide cream 0.025

VII Very low potency Topicals, which contain hydrocortisone acetate

^b

in 1.0% and 2.5% concentrations. Also topicals with dexamethasone

^b

, prednisolone

^b

and methylprednisolone

^b

.

aOptimized (augmented) vehicle contributes to the product’s potency. Some generic products now have augmented vehicles. Generics without augmentation should not be expected to have the same biological or clinical potency as augmented generic or augmented brand-name preparations.

bNonfluorinated steroid preparations.

cHydrocortisone products with side chains that enhance potency. These should not be confused with group VII products of hydrocortisone acetate.

Brand-name products are listed in Table 1 because these were used in the original vasoconstrictor assays.

Although generic equivalent products may show the same biological and clinical equivalency, studies of some generic products have shown as little as 25% of expected potency.

Modified from Stoughton RB, Cornell, RC. Semin Dermatol 6:72–76, 1987, and from refs. 4,6,9.

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appearance, control itching, and reduce the overall need for active medication. The emol- lient base must have enough occlusive property to help the skin surface retain water con- tent. At the same time, it must be cosmetically acceptable. Two products valuable for general use on dry skin are Original Formula Eucerin

^®

Cream and Cetaphil

^®

Moisturizing Cream. These are available also in lotion form. Initially, patients should start with the more lubricating cream base. Later, when the skin is hydrated, the lighter lotions can be introduced for daytime use. These should be applied in a general fashion and over any top- ical steroids after the shower, then once or twice more during the day.

Enhancers

Salicylic acid 3 to 6% in petrolatum or in a hydrophilic cream base can be used to remove heavy scale that otherwise impedes topical treatment. Systemic absorption with extensive use could lead to salicylism in children, persons on salicylates, or persons with compromised renal function. Combined use with topical steroids can increase absorption of the steroid by two- to threefold. This is probably mediated by the keratolytic action.

Urea containing creams and lotions are also available in 10 to 40% concentrations both by prescription and over the counter (OTC). Urea can double the penetration of some topical corticoids such as hydrocortisone. This effect is unreliable however, and some steroids are markedly inhibited.

Discussion of other topical medications such as topical antibiotics, retinoids, and macrolactams is covered in other chapters under the specific diseases they are used to treat. A discussion about antipruritic ingredients, however, may be of value here.

A plethora of OTC preparations are marketed for the symptomatic relief of pruritus.

Most of these products contain either a topical caine anesthetic or a topical antihistamine that acts as a local topical anesthetic. The most common active ingredients are benzocaine and diphenhydramine, both of which have a fairly high sensitizing potential when used on abraded or dermatitic skin. Even more important than the potential local reaction is the fact that benzocaine is capable of inducing broad cross-sensitivity to hair, fabric, and leather dyes, sulfonamide-based medications, and sunscreen agents.

Hypersensitivity to topical antihistamines will often result in a generalized delayed- type reaction upon systemic administration, and with topical sensitization to antihista- mines of the ethylenediamine group (pyribenzamine, antistine, phenergan) generalized cross-reactions with aminophylline are reported. Use of these for symptomatic relief of pruritus is not recommended.

Pramoxine, a local anesthetic that has proven to have very low sensitizing potential with topical use, is available OTC in cream, lotion, gel, and spray preparations. Also avail- able by prescription are a 2.5% hydrocortisone cream and lotion with pramoxine in the formulation.

Also recently marketed by prescription is a cream product that contains 5% doxepin

hydrochloride. Use of this product should be limited to local areas, and caution is espe-

cially important if there is any interruption of the epidermis. Significant percutaneous

absorption may occur, with attendant drowsiness and anticholinergic side effects. Use in

infants and preadolescents is not recommended.

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Finally, there are time-tested antipruritics, including menthol and camphor, which can be compounded with most topical steroids and most bases. These additives act as counter- irritants to relieve the itch. Menthol is usually added in a concentration of 0.025%, while camphor is typically used in 0.05 to 1.0% concentrations.

Systemic Steroid Therapy

Systemic steroid therapy will be discussed under specific disease entities. There are however some general concepts and precautions that should be mentioned.

1. Never commit a patient to systemic steroids without a firm diagnosis, especially if a referral is anticipated. This can make a dermatologist’s task virtually impos- sible.

2. Once a decision is made to use systemic corticoids, use enough to get the job done. There is lower risk with higher doses that achieve rapid control, rather than prolonged administration of low doses while chasing after the disease process.

3. Systemic steroids can result in severe withdrawal flares in some cases of psoria- sis and atopic dermatitis. In psoriasis, these can, on rare occasion, be life-threat- ening. Because both diseases are chronic and are only temporarily improved by corticoids, avoid their use and defer to a dermatologic consultant.

4. Use short-acting oral steroids whenever possible.

Intralesional Steroid Therapy

Injection of dilute solutions of corticosteroids into local skin lesions can result in com- plete clearing for months or years. This treatment is valuable for management of limited stable psoriasis, lichen simplex chronicus, alopecia areata, and focal lesions of hyper- trophic lichen planus, to mention a few.

The authors recommend triamcinolone acetonide exclusively. Other preparations tend to cause more skin atrophy. Whenever possible, dilute the solution to 2.5 mg/cc with physiologic saline, as higher concentrations increase the risk of side effects. Injec- tions should be done only with a control syringe using a 30 gage needle, withdrawing each time to prevent intravascular or lymphatic injection. Injections should be made into the high dermis, which raises a wheal. Deeper injections are less effective and increase the risk of subcutaneous atrophy. Injections into the scalp should be done with great caution because of possible embolization of this crystalline drug to the retinal artery with resulting blindness. Limit patients to a total of 10 mg of triamcinolone acetonide in any given 1-month period and try to keep the injections to an absolute minimum to minimize systemic side effects.

Antihistamines

Antihistamines are of only moderate value compared with topical medications and are mainly used for their sedative effect, except in the treatment of urticaria and related dis- orders of histamine release. Systemic use of antihistamines will be covered in depth in the section on urticaria.

Mastery of these basic elements will make you more confident and accurate in diag-

nosing and treating common skin conditions.

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ANSWERS TO CLINICAL APPLICATION QUESTIONS History Review

An 11-month-old infant presents at your office with an intensely pruritic generalized atopic dermatitis with multiple areas of excoriation and lichenification in some flexor locations. The eruption spares only the diaper area, the palms, and the soles. Most skin regions are dry and fissured.

1. Should you treat this patient with topical steroids, and if so, what type of topical steroids?

Answer: Atopic dermatitis is highly responsive to topical steroids.

Use the lowest-potency preparation that is effective for this patient. Begin with group VII preparations such as 1 to 2.5% hydrocortisone acetate in an emol- lient cream base. If this is ineffective, a trial of the next higher potency class is indicated. Because children have a high ratio of skin surface area to weight, higher- potency steroids are more likely to produce systemic effects such as growth retar- dation or adrenal suppression.

2. Should you treat this patient with systemic steroids, and if so, what type of systemic steroids?

Answer: No. Topical steroids are effective treatment with much less risk of growth retardation or adrenal suppression. If low-potency topical steroid treat- ment is not effective, dermatologic consultation is indicated.

3. Should you apply occlusive dressings in this patient over the affected areas, and if so, what type of occlusive dressings?

Answer: No. Occlusive dressings markedly increase systemic absorption of topical steroids and create a special risk to infants with generalized dermatitis.

Also, occlusive dressings promote secondary infection, which may aggravate the eczema.

4. Should you treat this patient with an emollient, and if so, why?

Answer: Dry skin can precipitate flares of atopic dermatitis. Proper use of emol- lients has a steroid-sparing effect. Often emollients will make a lower-potency steroid more effective and prevent relapse of the eczema in areas that have cleared with treatment.

Dermatologic treatment usually involves the use of topical therapy, which is a disci- pline unto itself. This form of treatment was primarily an art until about 20 years ago.

4 Therapy