Aveneu Park, Starling, Australia

The in skin disorders are, found to be, the

The skin (Figure
32-1) is subject to a very wide range of lesions. Some may be characteristic of
specific systemic diseases and fade as the disease regresses. Some are caused
by specific local infections and are best treated by the appropriate
antimicrobial, and Antifungals.

The skin is also
subject to damage from environmental hazards. Excessive or prolonged exposure
to solar radiation is associated with degenerative changes in the skin
(premature ageing of the skin or photoageing), actinic (solar) keratoses (which
are risk factors or precursors of skin cancers), and malignant neoplasms of the
skin.

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Many skin
disorders are side-effects of therapeutic and other agents, ranging from mild
hypersensitivity to the life-threatening Stevens-Johnson syndrome or toxic
epidermal necrolysis. There also remains a wide range of skin disorders whose
etiology is poorly understood.

 

Figure 32-1 Anatomy of skin

 

 

 

 

 

 

 

 

 

 

For drugs that
are applied topically, the vehicle and formulation may be as important as the
active drug. Indeed, some cream and ointment bases are used alone for their
protective or emollient properties, while adverse effects of topical
preparations are sometimes attributed to constituents of the vehicle such as
stabilisers and preservatives.

 

The choice of formulation depends on the
skin condition being treated and the area affected. Lotions and gels are useful
for hairy areas. Creams (oil-in-water emulsions) have cooling and emollient
effects, are readily absorbed by the skin, and are used for acute and exudative
conditions. Ointments (water-in-oil emulsions) are more occlusive than creams and
are particularly suitable for chronic dry lesions. Pastes (powder incorporated
in an ointment basis) are less occlusive than ointments and are useful for
their protective properties and for their use on circumscribed lesions. Other
less frequently used formulations include applications, collodions, and dusting
powders.

 

Recently, immunosuppressants such as alefacept
and efalizumab have been approved for use in psoriasis and pimecrolimus for
eczema. However the most important immunosuppressant and anti-inflammatory
drugs used in skin disorders are, found to be, the corticosteroids

 

32.2 Commonly used terms with skin disorders

 

The distribution
and morphological description of the skin lesion (its shape, colour, and
surface characteristics) are important in the diagnosis of skin disorders.
There are many terms used to describe skin lesions are as follows;

 

1) Abscess–a
collection of pus in a cavity

2) Bulla (or
blister)–a fluid-filled circumscribed lesion larger than 0.5 cm in
diameter

3) Comedo–a plug
of keratin and sebum in a pilosebaceous follicle

4) Ecchymosis–an
extravasation of blood into the skin

5) Erythema–red
coloration due to vascular dilatation

6) Fissure–a slit
through the whole thickness of the skin

7) Horn–a
thickening of the skin that is taller than it is broad

8) Keratosis–a
horny thickening of the skin

9) Lichenification–hard,
thickened skin with increased markings

10) Macule–an
area of altered colour or texture with no elevation above the surface of the             surrounding
skin

11) Nodule–a
dome-shaped or spherical-shaped, solid lesion, usually more than 0.5 cm in
diameter and depth

12) Papilloma–a
nipple-like mass

13) Papule–a
raised solid lesion, usually less than 0.5 cm in diameter

14) Petechia–a
pinhead-sized macule of blood in the skin

15) Plaque–a
raised, flat-topped, circumscribed lesion, usually larger than 2 cm in diameter but with no substantial depth

16) Purpura–a
macule of blood in the skin, larger than a petechia

17) Pustule–an
accumulation of pus in the skin

18) Scale–a flat
plate or flake of stratum corneum

19) Stria–a
streak-like, linear, atrophic lesion, pink, purple, or white in colour

20) Telangiectasia–a
visible dilatation of small cutaneous blood vessels

21) Vesicle–a
fluid-filled circumscribed lesion less than 0.5 cm in diameter

22) Wheal–an
elevated, white, compressible area of oedema often surrounded by a red      flare.

 

This session
describes some drugs used in the management of skin disorders. Treatment may
include topical and/or systemic drug therapy, although the pharmacology of many
of the drugs used in dermatology is poorly understood. Physical methods such as
cryotherapy, UV radiation, radiotherapy, and surgery also have a role.

 

32.3 Traditional drugs and the skin

 

Drugs with a
traditional place in the treatment of skin disorders include coal tar,
dithranol, ichthammol, and urea, as well as keratolytics such as benzoyl peroxide and salicylic acid.

 

32.3.1 Dithranol – Dithranol is used in the treatment of sub acute
and chronic psoriasis, usually in one of two ways.

 Conventional treatment is commonly started with an ointment or
paste containing 0.1% dithranol (0.05% in very fair patients) applied for a few
hours; the strength is gradually increased as necessary to 0.5%, occasionally
to 1%, and the duration of contact extended to overnight periods or longer. The
preparation is sparingly and accurately applied to the lesions only. If, on
initial treatment, lesions spread or excessive irritation occurs, the
concentration of dithranol or the frequency of application should be reduced;
if necessary, treatment should be stopped. After each treatment period the
patient should bathe or shower to remove any residual dithranol.

Dithranol may
cause a burning sensation especially on perilesional skin. Patients with fair
skin may be more sensitive than those with dark skin. It is irritant to the
eyes and mucous membranes. Use on the face, skin flexures, and genitals should
be avoided. Hands should be washed after use.

Dithranol should
not be used for acute or pustular psoriasis or on inflamed skin. It stains
skin, hair, some fabrics, plastics, and enamel. Staining of bathroom ware may
be less of a problem with creams than ointments. Stains on skin and hair slowly
disappear on cessation of treatment.

 

32.3.2 Urea – Urea promotes hydration and is mainly
applied topically in the treatment of ichthyosis and hyperkeratotic skin
disorders. Used intravenously it has osmotic diuretic properties similar to
mannitol and has been used in the treatment of acute increases in intracranial
pressure, due to cerebral oedema, and to decrease intra-ocular pressure in
acute glaucoma, but has been largely superseded by mannitol. Urea has also been
given intra-amniotically for the termination of pregnancy.

When applied
topically urea has hydrating and keratolytic properties. In the management of
ichthyosis and other dry skin disorders it is applied in creams or lotions
containing 5 to 25% urea. A preparation containing 40% may be used for nail
destruction.

Urea is fairly
rapidly absorbed from the gastrointestinal tract but causes gastrointestinal
irritation. Urea is distributed into extra cellular and intracellular fluids
including lymph, bile, CSF, and blood. It is reported to cross the placenta,
and penetrate the eye. It is excreted unchanged in the urine.

Topical
application of urea may be irritant to sensitive skin.

 

32.3.3 Benzoyl peroxide – Benzoyl peroxide has mild keratolytic properties. Its antimicrobial action
is probably due to its oxidizing effect and activity has been reported against Staphylococcus
epidermidis and Propionibacterium
acnes. It is used mainly in the treatment of
acne, in topical preparations usually containing 2.5 to 10%, sometimes with
other antimicrobials. It has been used similarly in the treatment of fungal
skin infections, such as tinea pedis although other drugs are usually
preferred. A 20% lotion has been applied every 8 to 12 hours in the treatment
of decubitus or stasis ulcers. Strengths are expressed as anhydrous benzoyl
peroxide although it is employed in a hydrous form for safety

Benzoyl peroxide
may explode if subjected to grinding, percussion, or heat. Hydrous benzoyl
peroxide containing water to reduce the risk of explosion may still explode if
exposed to temperatures higher than 60 degrees or cause fires in the presence
of reducing substances.

Topical
application of benzoyl peroxide may produce skin irritation, particularly on
beginning treatment. In some patients the irritation may require reduced
frequency of application or temporary suspension of treatment. Skin dryness,
peeling, rash, and transient local oedema may also occur. Contact sensitisation
has been reported in some patients using preparations containing benzoyl
peroxide. Caution is required when applying it near the eyes, the mouth and
other mucous membranes, and to the neck and other sensitive areas. Patients
should be alerted to benzoyl peroxide’s bleaching property.

 

32.3.4 Salicylic acid – Salicylic acid has keratolytic
properties and is applied topically in the treatment of hyperkeratotic and
scaling skin conditions such as dandruff and seborrhoeic dermatitis,
ichthyosis, psoriasis, and acne. Initially a concentration of about 2% is used,
increased to about 6% if necessary, though a wider range of concentrations has
been used. It is often used with other drugs, notably coal tar.

Preparations
containing up to 60% salicylic acid have been used as a caustic for the removal of plantar warts, corns, or calluses.

Salicylic acid
also possesses fungicidal
properties and is used topically in the treatment of dermatophyte skin
infections; propyl salicylate and bromosalicylic acid have been used similarly.

Zinc salicylate
has been used similarly to salicylic acid in the treatment of seborrhoeic
dermatitis and acne.

Salicylic acid is
a mild irritant and application of salicylic acid preparations to the skin may
cause dermatitis. It is readily absorbed through the skin and symptoms of acute
systemic salicylate poisoning have been reported after excessive use; deaths
have occurred, mainly in children. To minimize absorption following topical
application salicylic acid should not be used for prolonged periods, in high
concentrations, on large areas of the body, or on inflamed or broken skin.
Contact with mouth, eyes, and other mucous membranes should be avoided. It
should also be used with care on the extremities of patients with impaired
peripheral circulation or diabetes; caution has also been suggested for the use
of caustic preparations in patients with significant peripheral neuropathy.

 

32.4 Photosensitisers 

 

Photosensitisers such
as the psoralen methoxsalen, vitamin D analogues such as calcipotriol, and the
vitamin A analogues (retinoids) such as acitretin, isotretinoin, and tretinoin
have an important role in certain skin disorders.

 

32.4.1 Calcipotriol – is a vitamin D3 derivative. In vitro it appears to induce
differentiation and to suppress proliferation of keratinocytes.

Calcipotriol is
used in a cream or ointment for the management of plaque psoriasis and as a
solution in the management of scalp psoriasis; the concentration of
calcipotriol used is 0.005%. In adults, applications should be made once or
twice daily. No more than 100 g of cream or ointment, or 60 mL of
scalp solution, should be applied in one week. If both are used, the limit is
60 g of cream or ointment with 30 mL of scalp solution, or 30 g
of cream or ointment with 60 mL of scalp solution.

The most frequent
adverse effect associated with calcipotriol is skin irritation and it should
not therefore be applied to the facial area. Symptoms may include burning,
itching, erythema, and dry skin, but discontinuation of therapy is seldom
necessary. Aggravation of psoriasis may occur. Hypercalcaemia that is rapidly
reversible on withdrawal has occurred during treatment with calcipotriol and it
should not be used in patients with disorders of calcium metabolism. Other rare
adverse effects may include skin atrophy and photosensitivity.

 

32.4.2 Acitretin – is
a retinoid. It is a metabolite of etretinate. Acitretin is used by mouth in the
treatment of severe psoriasis resistant to other forms of therapy,
palmo-plantar pustular psoriasis, and in severe congenital ichthyosis and
Darier’s disease (keratosis follicularis).

Acitretin is
absorbed from the gastrointestinal tract and peak plasma concentrations have
been obtained 1 to 6 hours after oral administration. Oral bioavailability may
be increased by administration with food. Acitretin is highly bound to plasma
proteins. It is metabolised to 13-cis-acitretin.

Acitretin has a
relatively short half-life, but etretinate, which has a much longer half-life,
has been detected in the plasma of some patients receiving acitretin.
Recommendations vary slightly in different countries but pregnancy should be
avoided for at least 2 to 3 years after treatment has been withdrawn and
patients should not donate blood for at least 1 to 3 years after cessation of
therapy. Female patients should avoid alcohol during treatment with acitretin
and for 2 months after stopping treatment

 

32.4.3 Isotrtinoin – is a retinoid. It is the
cis configuration of tretinoin,
which is the acid form of vitamin A. Isotretinoin is given by mouth for the
treatment of severe acne that has not responded to other measures; it is also
applied topically in milder forms of acne. It is not indicated for
uncomplicated adolescent acne. Isotretinoin has also been tried in a number of
other skin disorders and in some forms of neoplastic disease.

Isotretinoin is
absorbed from the gastrointestinal tract and absorption may be increased by
food. Minimal systemic absorption occurs following topical application. Peak
plasma concentrations occur 1 to 4 hours after oral doses. Oral bioavailability
is low, possibly due to metabolism in the gut wall and first-pass metabolism in
the liver. Isotretinoin is highly bound to plasma proteins. It is metabolised
in the liver to its major metabolite 4-oxo-isotretinoin; there is also some
isomerisation of isotretinoin to tretinoin. Isotretinoin, tretinoin, and their
metabolites undergo enterohepatic recycling. The terminal elimination half-life
of isotretinoin is 10 to 20 hours, while that of the 4-oxo metabolite may be up
to 50 hours; return to physiological levels of retinoids takes about 2 weeks
after stopping therapy. Equal amounts of a dose appear in the faeces, mainly as
unchanged drug, and in the urine as metabolites.

 

32.4.4 Tretinoin – is
used primarily in the topical treatment of acne vulgaris when comedones, papules, and pustules predominate.
It appears to stimulate mitosis and turnover of follicular epithelial cells and
reduce their cohesiveness thereby facilitating the extrusion of existing
comedones and preventing the formation of new ones. It also appears to have a
thinning effect on the stratum corneum. Tretinoin is applied as a cream, gel,
or alcoholic solution, usually containing 0.01 to 0.1%. The skin should be
cleansed to remove excessive oiliness and dried 15 to 30 minutes before
applying tretinoin lightly, once or twice daily according to response and
irritation; some patients may require less frequent applications. Other topical
preparations (including skin moisturisers) should not be applied at the same
time as tretinoin is applied, and caution is required if other local irritants
are used concurrently. There may be apparent exacerbations of the acne during
early treatment and a therapeutic response may not be evident for 6 to 8 weeks.
When the condition has resolved maintenance therapy should be less frequent.

 

 

 

32.5 Skin protective drugs

 

Drugs with
primarily a protective function
include calamine, starch, talc, titanium dioxide, and zinc oxide. Some drugs,
for example ammonium lactate and sodium pidolate, have humectant properties and are used in topical moisturising
preparations.

 

 

Other substances
used to protect against sunlight
are the sunscreens. These are of 2 types: chemical (absorbent or organic) agents that because of their
chromophore groups absorb a particular range of wavelengths within the ultra
violet (UV) spectrum and physical
(reflective or inorganic) agents that are opaque and reflect both UVA and UVB
radiation.

 

Compounds used as
chemical sunscreens include the amino benzoates such as aminobenzoic acid,
anthranilates such as meradimate, benzophenones such as oxybenzone, camphor
derivatives such as enzacamene, camphorsulfonic acid derivatives such as
ecamsule, cinnamates such as octinoxate, dibenzoylmethanes such as avobenzone,
and salicylates such as octil salicylate. Benzophenones absorb both UVA and UVB
light; anthranilates, camphorsulfonic acid derivatives, and dibenzoylmethanes
absorb UVA light; the other compounds absorb only UVB light. Trolamine
salicylate is a chemical sunscreen that is also used as a topical analgesic.
Physical sunscreens include titanium dioxide and zinc oxide. Many of the
available products combine sunscreens from the different groups in order to
widen the protection afforded. Other agents used as physical sunscreens include
calcium carbonate, kaolin, magnesium oxide, red veterinary petroleum, and talc.

 

32.5.1 Calamine
– is a mixture of zinc oxide
(ZnO) with about 0.5% iron (III) oxide (Fe2O3). It is the
main ingredient in calamine lotion
and is used as an antipruritic (anti-itching agent) to treat mild pruritic
conditions such as sunburn, eczema, rashes, poison ivy, chickenpox, insect
bites and stingsIt is also used as a mild antiseptic to prevent infections that
can be caused by scratching the affected area, and an astringent to dry weeping
or oozing blisters and acne abscesses

 

32.5.2 Amino benzoic acid -is used by topical application as a
sunscreen.  Amino benzoic acid and its
derivatives effectively absorb light throughout the UVB range but absorb little
or no UVA light. Aminobenzoate sunscreens may therefore be used to prevent
sunburn, but are unlikely to prevent drug-related or other photosensitivity
reactions associated with UVA light; combination with a benzophenone may give
some added protection against such photosensitivity.

Amino benzoic
acid has sometimes been included as a member of the vitamin-B group, but
deficiency of aminobenzoic acid in man or animals has not been demonstrated.

Aminobenzoate
sunscreens should not be used by those with a history of photosensitivity or
hypersensitivity reactions to chemically related drugs such as sulfonamides,
thiazide diuretics, and certain local anaesthetics, particularly benzocaine.
Aminobenzoic acid may stain clothing.

 

32.5.3 Meradimate- is
used as a sunscreen. It is effective against UVA light.

 

32.5.4 Oxybenzone- is a substituted benzophenone used by
topical application as a sunscreen. Benzophenones effectively absorb light
throughout the UVB range (wavelengths 290 to 320 nm) and also absorb some
UVA light with wavelengths of 320 to about 360 nm and some UVC light with
wavelengths of about 250 to 290 nm. Benzophenones may therefore be used to
prevent sunburn and may also provide some protection against drug-related or
other photosensitivity reactions associated with UVA light; in practice they
are usually combined with a sunscreen from another group.

Contact and photo
contact allergic dermatitis has occasionally been reported following the
topical administration of benzophenone sunscreens.

 

32.5.5 Enzacamene – is a
camphor derivative used as a sunscreen. It is effective against UVB light.

 

32.5.6 Ecamsule- is a
camphorsulfonic acid derivative, is used as a sunscreen. It is effective
against UVA light

 

32.5.7 Octinoxate- a
substituted cinnamate is used by topical application as a sunscreen. Cinnamate
sunscreens effectively absorb light throughout the UVB range but absorb little
or no UVA light. Cinnamate sunscreens may therefore be used to prevent sunburn
but are unlikely to prevent drug-related or other photosensitivity reactions
associated with UVA light; combination with a benzophenone may give some added
protection against such photosensitivity. Cinnamates may occasionally produce
photosensitivity reactions.

 

32.6 Drugs which increases the
pigmentation

 

Drugs used to increase pigmentation include
dihydroxyacetone, methoxsalen, and trioxysalen. Those used to reduce pigmentation include
hydroquinone, mequinol, and monobenzone.

 

32.6.1 Dihydroxyacetone

 

Application to
the skin of preparations containing dihydroxyacetone slowly produces a brown
coloration similar to that caused by exposure to the sun, probably due to a
reaction with the amino acids of the skin.

A single
application may give rise to a patchy appearance; progressive darkening of the
skin results from repeated use until a point is reached when the maximum effect
is achieved. If the treatment is stopped the colour starts to fade after about
2 days and disappears completely within 8 to 14 days as the external epidermal
cells are lost by normal attrition.

Skin irritation
from dihydroxyacetone occurs rarely; rashes and allergic dermatitis have been
reported. Contact with eyes, abraded skin, and clothing should be avoided.

 

32.6.2 Methoxsalen- a
psoralen, is a constituent of the fruits of Ammi majus. It is a photosensitiser markedly
increasing skin reactivity to long-wavelength ultraviolet radiation (320 to
400 nm), an effect used in photochemotherapy or PUVA psoralen (P) and
high-intensity long-wavelength UVA irradiation. In the presence of UVA
methoxsalen bonds with DNA, inhibiting DNA synthesis and cell division, and can
lead to cell injury. Recovery from the cell injury may be followed by increased
melanisation of the epidermis. Methoxsalen may also increase pigmentation by an
action on melanocytes. Methoxsalen should not
be given to patients with diseases associated with light sensitivity such as
porphyria, although it is used with care to decrease some patients’ sensitivity
to sunlight. Other contra-indications include aphakia, melanoma or a history of
melanoma, and invasive squamous cell carcinoma. It is generally recommended
that PUVA therapy should not be used in children. Methoxsalen should be used
with caution in patients with hepatic insufficiency.

 

 

32.6.3 Trioxysalen – a
psoralen is a photosensitiser used similarly to methoxsalen in
photochemotherapy or PUVA therapy. Trioxysalen may also be used topically in
the PUVA treatment of psoriasis.

 

32.7 Humectants

 

Some drugs, for
example ammonium lactate and sodium pidolate, have humectant properties and are used in topical moisturising
preparations. A humectant is a substance used primarily in foods and
cosmetic products to help retain moisture. These substances are called hygroscopic, which means that they
are able to absorb ambient water. Some humectant additives are beneficial when
consumed or used. Others, particularly in some foods, are less helpful, may cause
abdominal distress, and should probably be avoided

 

32.7.1 Ammonium lactate – Ammonium lactate is a humectant applied as a cream or lotion containing 12%
lactic acid neutralised with ammonium hydroxide. It is used in the treatment of
dry scaly conditions of the skin including ichthyosis.  

 

32.7.2 Sodium pidolate – Sodium pidolate is used as a humectant. It is applied topically as a cream
or lotion, often in multi-ingredient preparations, in the treatment of dry skin
disorders. 

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