A Textbook of Clinical Pharmacology and Therapeutics

Uses

The use of systemic glucocorticosteroids (e.g. oral prednisolone)
is limited to serious disorders such as pemphigus or refractory
exfoliative dermatitis (e.g. Stevens Johnson syndrome). Topical
glucocorticosteroids are widely used and effective in treating
eczema, lichen planus, discoid lupus erythematosus, lichen sim-
plex chronicus and palmar plantar pustulosis, but rarely in pso-
riasis. The symptoms of eczema are rapidly suppressed, but
these drugs do not treat the cause. In the presence of infection,
they are combined with an antimicrobial agent. The lowest
potency glucocorticosteroid preparation that will control the
disease is preferred. Occlusive dressings should be used only in
the short term (two to three days) and increase potency consid-
erably. Potent fluorinated glucocorticosteroids should not be
used on the face because they cause dermatitis medicamentosa.
Many preparations are available, some of which are listed in
descending order of anti-inflammatory potency in Table 51.1.

Adverse effeccts of cutaneoulsly applied
glucocorticosteroids

These include the following:

• hypothalamic–pituitary–adrenal suppression where very
  potent drugs are used long term on large areas of skin or
  when systemic absorption is increased under occlusive
  dressing;


• spread of local infection – bacterial or fungal;


• atrophic striae;


• depigmentation and vellus hair formation;


• perioral dermatitis when applied to the face;


• rebound exacerbation of disease (e.g. pustular psoriasis)
  when treatment is stopped;


• exacerbation of glaucoma if applied to the eyelids;


• contact dermatitis (rare);


• hirsutism and acne if systemic absorption is very high.

PSORIASIS

Psoriasis occurs in approximately 2% of the population. Its cause

is unknown and no treatment is curative. The skin lesions are

characterized by epidermal thickening and scaling due to

increased epidermal undifferentiated cell proliferation with

abnormal keratin. Figure 51.3 shows an algorithm for treatment.

Therapy in mild cases consists of reassurance and a simple

emollient cream. More resistant cases are treated with a kera-

tolytic, e.g. salicylic acid,coal tarordithranolapplied accur-

ately to the lesions. Topical and systemic steroids are reserved

for cases that do not respond to these simple remedies and

their use should be monitored by a specialist, as they can

worsen the disease in some patients (e.g. pustular psoriasis on

stopping treatment). Calcitriol(a vitamin D analogue) is effec-

tive topically. In some cases, therapy with PUVA (see below) is

effective. Refractory cases are treated with oral retinoids (e.g.

acetretin).

Occasionally refractory cases justify immunosuppression

withmethotrexate(Chapters 48 and 50), but chronic use can

cause cirrhosis. Potential recipients need to be warned about

this and their liver function must be monitored meticulously.

Ciclosporinis an alternative (Chapter 50), but causes hyper-

tension and nephrotoxicity. Regular monitoring of blood pres-

sure and plasma ciclosporin concentration is essential.

Recently, the use of biological agents (alefacept,etanercept,

efalizumab,infliximab) has been found to produce good

remissions in otherwise refractory psoriasis (see Table 51.2);

these agents are discussed more fully in Chapter 50. Second-

line therapies (phototherapy or systemic drugs) should only

be used under the supervision of a dermatologist.

CALCIPOTRIOL (1-α, 24-DIHYDROXYVITAMIN D 3 )

This analogue of vitamin D 3 is used as a cream applied to mild

to moderate psoriasis. Vitamin D receptors are present in ker-

atinocytes, T and B lymphocytes and dermal fibroblasts of

psoriatics, and the stimulation of vitamin D receptors on ker-

atinocytes inhibits proliferation and differentiation. Adverse

effects include local irritation, facial and perioral dermatitis,

and possible hypercalcaemia and hypertriglyceridaemia if

used too extensively. It should not be used in pregnancy.

PSORALEN WITH ULTRAVIOLET A LIGHT

Psoralenwith ultraviolet A light (PUVA) is a well-established

but somewhat inconvenient therapy for chronic plaque psor-

iasis. Psoralens intercalate DNA bases and, when activated by

light, produce highly reactive oxygen species which sensitize

the skin to the cytotoxic effects of long-wave UVA (320–

400 nm wavelength) radiation. Psoralenis taken orally two

hours before phototherapy, or applied topically immediately

before phototherapy; the usual course lasts for four to six

weeks. Skin burning and ageing, cataracts and skin cancer are

potential complications, especially with the higher total doses

of UVA. Sunglasses are worn during UVA exposure in order to

reduce the risk of cataract formation, if the psoralenhas been

administered orally. Technological advances in psoralens and

414 DRUGS AND THE SKIN

Table 51.1 :Topical glucocorticosteroids and their anti-inflammatory potency

Potency Drug and strength

Extremely potent Clobetasol (0.05%)

Halcinonide (0.1%)

Diflucortolone (0.3%)

Potent Beclometasone (0.025%)

Budesonide (0.025%)

Fluocinolone (0.025%)

Fluocinonide (0.05%)

Moderately potent Clobetasone (0.05%)

Flurandrenolone (0.0125%)

Mild Hydrocortisone (0.5–2.5%)

Alclometasone (0.05%)

Methylprednisolone (0.25%)