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192 Chapter 8 Inflammation and the skin: dermatitis, psoriasis, and acne
Box 8.3 Development and treatment of atopic dermatitis
down of the inammatory response, through decreased
recruitment of cells involved in the immune response,
and reduced levels of inammatory mediators.
Calcineurin inhibitors such as tacrolimus and
pimecrolimus also modify the immune response, but
have a dierent mode of action. Calcineurin is a
phosphatase enzyme which dephosphorylates
transcription factors in the cytosol belonging to the
NFAT family (nuclear factor of activated T-cells).
Phosphorylated NFAT is retained in the cytosol, but
8.4.3 Topical calcineurin inhibitors
e calcineurin inhibitors tacrolimus and pimecrolimus
are a relatively new class of topical immunosuppressant
drugs used in dermatitis. eir use is usually restricted to
more severe cases, and only then when other treatments
have failed.
Calcineurin inhibitors prevent expression of proinammatory genes, reducing activation of T-cells, and
Table 8.2 Potency of steroids in topical preparations for
dermatitis
Potency Drug
Mild Hydrocortisone 0.1–2.5%
Hydrocortisone acetate 1%
Fluocinolone acetonide 0.0025%
Moderate Betamethasone valerate 0.025%
Clobetasone butyratea 0.05%
Fluocinolone acetonide 0.00625%
Desonide 0.05%
Triamcinolone 0.02%
Potent Betamethasone valerate 0.1%
Hydrocortisone butyrate 0.1%
Methylprednisolone 0.1%
Very potent Clobetasol propionatea 0.05%
Diflucortolone valerate 0.3%
Halcinonide 0.1%
a
Note that only small structural differences can have a big impact on the
potency of corticosteroids; clobetasol and clobetasone differ only in the
functional groups at C-11, which are C–OH and C=O, respectively, yet
this results in a change from a moderately potent steroid to one that is
very potent.
when dephosphorylated by calcineurin, it undergoes a
conformational change exposing a nuclear binding site.
NFAT can then enter the nucleus to alter the expression
of genes encoding proteins involved in T-cell activation
and the immune response. e immediate targets for
calcineurin inhibitors are cytosolic proteins called
immunophilins. e drug–immunophilin complex
thus formed binds to, and inhibits, calcineurin,
ensuring that NFAT remains in the phosphorylated
state and so preventing gene transcription.
so dampening down the inammatory processes
underlying dermatitis (see Box 8.3 for a more detailed
account of their mode of action). ese
immunosuppressants are useful in other clinical
situations (e.g. tacrolimus is used to suppress organ
transplant rejection).
Calcineurin inhibitors are used for short-term treatment
of patients over 2 years old who do not respond to
emollients and topical corticosteroids. Applied topically
they do not appear to have the unwanted eects on the
skin that are associated with steroids (see above). Systemic
eects also appear minimal, although the long-term safety
of these relatively new drugs has yet to be fully evaluated.
8.4.4 Topical antibacterials and antifungals
In addition to medication directly targeting the
dermatitis process, the use of topical antibiotics may
be required as open lesions can lead to local
infections. Compound preparations combining a
steroid with an antibacterial are available. Such
preparations are most suitable for short-term
(7–10 days) treatment.
Topical application of antifungal agents, including the
imidazole ketoconazole, can reduce Pityosporum ovale
growth on the skin and is useful in the treatment and
prophylaxis of seborrhoeic dermatitis. e drug is
fungistatic, interfering with the structure of the fungal
cell membrane to inhibit replication. Ketoconazole is
available in the form of a cream and as shampoo.
8.6 Treatment of psoriasis 193
8.5 Psoriasis
Psoriasis is a chronic inammatory disease which
primarily aects the skin, but which, in 10–15% of
suerers, is also associated with arthritis (psoriatic
arthritis) and can lead to permanent damage to joints.
Aected skin areas are characterized by epidermal
thickening and red itchy patches (psoriatic plaques),
which can be painful. e plaques develop silvery-white
scales at their surface, and bleeding may occur when
these are peeled away (Figure 8.3). Psoriasis can aect the
skin in any area of the body, but the outsides of knees and
elbows, trunk, and scalp are the most common sites. Nails
can also be aected, appearing pitted and yellow, and
lifting away from the skin.
Figure 8.3 Plaque psoriasis.
Skin appears thickened with raised red plaques that have silvery
scaly surfaces.
From Saxe N, Jessop S, Todd G, Handbook of Dermatology for Primary
Care (2nd edn), 2007. By permission of Oxford University Press.
e underlying pathology is an increased rate of
production and migration of keratinocytes, such that the
life cycle of cells is greatly speeded up, and can be as rapid
as 7 days compared with the normal 30 days (see Box 8.1).
e increased epidermal turnover accounts for the
thickening of the epidermal layer, and the appearance of
raised plaques due to the abundance of cells. e scales
are composed of dead skin cells. e dermal layer is also
aected, with capillaries being dilated and closer to the
surface. Psoriasis is an immune condition; psoriatic skin
has increased levels of inammatory mediators and cells
involved in the immune response, including Langerhans
cells (see Section 8.1) and T-lymphocytes.
Most sufferers of psoriasis are genetically predisposed
to the condition, which is then triggered by
environmental factors such as smoking, alcohol,
emotional stress, trauma to the skin, or bacterial
infection. Some drugs, including NSAIDs, -blockers,
lithium, and the rapid withdrawal of systemic
corticosteroids can also precipitate psoriasis in
predisposed individuals.
Psoriasis is a recurring condition, varying in severity from
minor localized patches to complete body coverage.
ere are a number of forms of the disease; by far the
most common is plaque psoriasis (or psoriasis vulgaris,
where ‘vulgaris’ means common) accounting for ~80% of
all cases. Other forms which aect specic areas, such as
the scalp, are also seen.
Psoriasis can have an enormous psychological impact on
the suerer and may lead to depression and loss of selfesteem. e chronic and recurrent nature of the disease
can make it a challenge to treat.
8.6 Treatment of psoriasis
Mild psoriasis can in many cases be treated solely with
emollient therapy. Where this proves insucient,
additional treatment targets the underlying
hyperproliferation of keratinocytes and inammatory
processes. Regimes must be individualized, taking into
account patient preference and severity of disease. Nonpharmacological interventions such as phototherapy may
also be considered.
8.6.1 Topical treatment of psoriasis
Emollients
ese have a crucial role in easing discomfort, by
rehydrating and restoring the barrier function of the skin
(see Section 8.4). ey should be used alongside more
specic interventions.
194 Chapter 8 Inflammation and the skin: dermatitis, psoriasis, and acne
Vitamin D analogues
Dihydroxy-vitamin D3 (calcitriol) and its synthetic
analogues calcipotriol and tacalcitol are the rst choice
for the long-term treatment of psoriasis. Applied
topically, they act at vitamin D receptors in the cytosol of
keratinocytes. ese are nuclear receptors (see Chapter 2,
Section 2.2.6) which when activated alter gene expression
to regulate cell growth and dierentiation within the
epidermis, and so normalize the rapid turnover of
keratinocytes which underlies psoriasis. ese drugs also
have a benecial immunosuppressant action, dampening
down the inammatory processes in aected skin by
reducing production of inammatory mediators such as
interleukin-2.
Vitamin D analogues do not smell or stain skin and
clothing, and therefore may be more acceptable than tar
or dithranol products (see below). erapeutic response
is slow to develop fully, taking up to 6 weeks. Local
adverse eects, including burning and irritation of the
skin, are common and are more likely with calcipotriol.
ese drugs should not be used in more inammatory
forms of psoriasis.
Corticosteroids
Topical corticosteroids in the form of creams, ointments,
and gels are widely used for short-term treatment of
psoriasis. eir immunosuppressive, anti-inammatory,
and anti-proliferative properties can result in early and
dramatic improvement. eir long-term use in a chronic
condition such as psoriasis, however, suers two major
drawbacks.
1) Tachyphylaxis—sudden drop in therapeutic eect
despite continued application. is may result from
true loss of ecacy, or from poor adherence, or a
combination of both.
2) Risk of serious side eects.
In the treatment of psoriasis, corticosteroids are most
eective when combined with other drugs, for instance
vitamin D analogues; the combination is more eective
than either drug alone and reduces corticosteroid use.
For further consideration of the use of corticosteroids, see
Section 8.4.2 and Chapter 9, Section 9.3.2.
Dithranol (anthralin)
Dithranol is eective in the treatment of psoriasis vulgaris
when applied to well-dened plaques with care being taken
to avoid irritating non-aected skin. It is not suitable for use
on the face or exures. Its mechanism of action is not fully
understood, but results in inhibition of keratinocyte
proliferation. e therapeutic response develops relatively
slowly, but lasts longer than that of corticosteroids, and
rebound exacerbations when treatment is halted are not
seen. Dithranol permanently stains skin, hair, and clothing
yellow, and is unpopular for this reason.
Coal tars
Coal tars are complex mixtures of thousands of aromatic
hydrocarbons. erapeutic tars have an apparent antiproliferative and anti-inammatory eect, although the
underlying mechanism is not clear. Crude coal tar, at
concentrations of 1–10%, is the most eective form, but it
is smelly and can be messy to use. e milder extracts of
coal tar in proprietary preparations are easier to apply but
are less eective, and improvement takes longer. ey can
be useful adjuncts to topical corticosteroids. Normal skin
is not aected by coal tar products, making them useful
for widespread small lesions, although irritation of
delicate skin and contact allergy can occur. Tar has an
anti-pruritic eect, and can also be used in dermatitis.
Salicylic acid
Salicylic acid has a keratolytic (peeling) action which is of
benet in the treatment of psoriasis, and aids the access
of other medications to the aected area. It is used most
often in the treatment of scalp psoriasis, and is commonly
combined in shampoos with other therapeutic agents,
such as tars.
Topical retinoids
Tazarotene is a retinoid (vitamin A derivative) used
topically in the treatment of mild to moderate psoriasis. Its
mode of action is not fully understood, but it is believed to
bind to the retinoid X and retinoic acid receptors. ese
are intracellular or nuclear receptors (see Chapter 2,
Section 2.2.6) which, when activated, interfere directly
with gene expression. e downstream consequences are:
• decreased keratinocyte dierentiation and proliferation
• decreased inammatory response
• reduced size and output of sebaceous glands.
Retinoids may also have antimicrobial properties which
are of particular benet in the treatment of acne (see
Section 8.8.1).
Tazarotene can produce local irritation, including
burning, itching, and stinging, but this is reduced when it
8.6 Treatment of psoriasis 195
is used in combination with a low- to medium-strength
topical corticosteroid. is can increase the ecacy of
both drugs; tazarotene is therefore a useful corticosteroidsparing agent.
Retinoids are teratogens, causing serious skeletal
deformities in fetuses. Although topical use results in only
tiny amounts of the active drug reaching the systemic
circulation, they should be avoided in pregnancy. (See
also discussion of oral retinoids below.)
8.6.2 Systemic treatment of psoriasis
Severe widespread psoriasis may necessitate systemic
therapy where phototherapy and topical treatments are
either not tolerated, or are followed by rapid relapse.
Methotrexate
e folate analogue methotrexate is used in moderate to
severe psoriasis that is not eectively treated by other
approaches. In adults of non-child-bearing potential, this
is often the rst-line systemic agent. Methotrexate is an
inhibitor of the enzyme dihydrofolate reductase, blocking
folate biosynthesis which is required for DNA synthesis.
e drug has long been used in cancer chemotherapy,
and rheumatoid arthritis, for its anti-proliferative eects
(see Chapter 9, Section 9.4, for more details of its mode of
action). e anti-proliferative action may also underlie
the benecial eect in psoriasis, although recent evidence
has pointed towards an immunosuppressive eect on
activated T-cells. Acute toxicity can occur due to the
eects on rapidly dividing cells, for instance those in the
bone marrow and mucosal linings. Gastrointestinal
bleeding, soreness of the mouth, and increased risk of
infection can result. Risk of toxicity is increased if taken
with drugs that inhibit its renal excretion, such as NSAIDs
and penicillins. In the treatment of psoriasis,
methotrexate is administered once weekly, either orally or
by injection; folic acid taken on the remaining days may
reduce side eects. Long-term use of methotrexate is
associated with hepatic cirrhosis, which necessitates liver
function monitoring. It is a teratogen and must be avoided
in pregnancy; men and women should use contraception
whilst receiving methotrexate, and for 3 months after
stopping. (For further details see Chapter 9, Section 9.4.)
Oral retinoids
e retinoid acitretin is taken orally in severe and
extensive psoriasis. It is most often combined with other
treatments and/or phototherapy (see below) so that UV
exposure can be reduced. A therapeutic eect is only seen
after 2–4 weeks. is presumably reects the time taken to
see alterations in gene expression in target cells, its likely
mechanism of action (see topical retinoids above).
Acitretin is a metabolite of etretinate which was used to
treat psoriasis until its withdrawal due to high risk of birth
defects. Etretinate is highly lipophilic, accumulating in
subcutaneous fat and giving rise to a very long
elimination half-life of around 120 days. Acitretin has a
reduced tendency to accumulate in tissues, and a half-life
of around 2 days. However, conversion of acitretin to
etretinate can occur in the body, and in particular has
been reported in the presence of alcohol; patients should
be advised not to drink alcohol whilst taking the drug.
Both acitretin and etretinate are serious teratogens (see
above). e possibility of pregnancy must be excluded at
the initiation of treatment with acitretin, while it is
ongoing, and for 3 years after stopping to exclude any
danger from etretinate which may have formed. Acitretin
is associated with hepatotoxicity and altered serum lipid
levels; cholesterol and triglyceride levels and liver
function must be monitored whilst treatment is ongoing.
Oral calcineurin inhibitors
e naturally occurring calcineurin inhibitor ciclosporin
is a potent immunosuppressant that blocks T-cell
activation and the immune response (see Box 8.3). It is a
rapid and highly eective oral treatment for psoriasis, but
its long-term use is restricted by nephrotoxicity and
hypertension, and so it is reserved for severe and
unresponsive cases. Risk of nephrotoxicity is increased by
a number of drugs including NSAIDs.
Biological agents
Biological agents are genetically engineered proteins that
target specic key mediators of the inammatory process
(see Chapter 9, Section 9.5). A number of these drugs are
used to treat severe plaque psoriasis, including
infliximab, adalimumab, and etanercept. ey are
directed against tumour necrosis factor-, a potent
inammatory cytokine central to the pathogenesis of
psoriasis. ese drugs are also used in the treatment of
rheumatoid arthritis, and are discussed in more detail in
Chapter 9, Section 9.5.1.
Ustekinumab and secukinumab are two further
biological agents used in the treatment of severe
psoriasis. Both drugs are fully humanized monoclonal
antibodies directed against specic interleukins centrally
196 Chapter 8 Inflammation and the skin: dermatitis, psoriasis, and acne
involved in inammation. Ustekinumab targets
interleukins 12 and 23, which are crucial to the activation
of T-cells. Secukinumab is directed against interleukin17a which is produced by activated T-cells. is cytokine
plays a number of key roles in coordinating the immune
response, which include stimulating the expression of
cyclo-oxygenase 2, the enzyme that catalyses the
formation of prostaglandin mediators of inammation.
All of these biological agents have been shown to have
excellent short- and long-term ecacy, and are generally
tolerated well, although increased risk of infection (e.g.
from latent tuberculosis or hepatitis B) is a possible and
serious side eect. Other adverse eects include nausea,
abdominal pain, and worsening heart failure. Antibodies
are administered as subcutaneous injection or intravenous
infusion, and are used in cases of severe plaque psoriasis
which has failed to respond to standard systemic treatment
and phototherapy, or where such therapies cannot be used.
8.7 Acne
Acne aects 80–90% of all adolescents, and accounts for
more physician visits than any other skin disease. It is a
disease of the sebaceous glands associated with the hair
follicles, and is characterized by blackheads, whiteheads,
pustules, and possible scarring. Areas of the skin most
aected are the face, chest, and back, where the density of
sebaceous glands is greatest.
Non-pharmacological treatment of psoriasis:
phototherapy and photochemotherapy
Exposure of psoriatic skin to UVB light has
immunosuppressive eects and improves symptoms.
Narrowband UVB light is preferable to broadband for
reasons of safety, notably the reduced risk of burning and
carcinogenic potential. Phototherapy can be used in
conjunction with the medications described above.
e alternative, photochemotherapy, involves treatment
with compounds called psoralens for 2 hours before
exposure to UVA light (psoralen + UVA, abbreviated to
PUVA treatment). Psoralens are natural mutagens, and
their photomodication induces apoptosis in the
epidermal layer by encouraging binding and crosslinking
of thymidine bases in DNA. Patients require multiple
treatments for long periods of time, and the increased risk
of developing skin cancers is a signicant problem.
Acne develops in a number of stages.
1. Hair follicles become blocked by an accumulation
of sebum and abnormal keratinization of the follicles,
leading to their enlargement, and formation of open
comedones or blackheads; the sebum darkens as it
oxidizes over time. A whitehead (closed comedo)
occurs when sebum is not exposed to air (Figure 8.4).
Hair
Skin surface
Sebum
Follicle
Sebaceous
gland
Normal follicle Closed comedo (whitehead)
Blackhead
Enlargement
of follicle
opening
Open comedo (blackhead) Pustule
Figure 8.4 Diseased hair follicles are the origin of blackheads, whiteheads,
and pustules.
Whitehead
Enlargement
of follicle
opening
Pustule
Enlargement
of follicle
opening
8.8 Drug treatment of acne 197
2. e plug disrupts the normal movement of hair, dead
skin cells, and sebum; these accumulate, and the
blocked follicle eventually ruptures.
3. e contents of the follicle are spilt onto the skin
leading to redness and an inammatory response.
4. Propionibacterium acnes, normally present in hair
follicles, causes local inflammation of the follicle
and dermis, and produces enzymes that digest
sebum, so increasing free fatty acid levels; the
8.8 Drug treatment of acne
Whilst not oering a cure, treatment for acne can
reduce severity and if started early enough can prevent
scarring. Treatment choice is based on whether or not
the acne is predominantly inammatory, as well as its
severity. Topical drugs are prevalent in treatment,
although some oral treatments are used. Table 8.3
details the site of action of drugs used in acne. Patients
need to be counselled on the correct use of medication
and advised that an improvement may not be seen for
several weeks.
products further irritate and inflame the skin.
Inflammatory lesions are known as papules and
pustules.
During puberty increased androgen levels result in
enlargement of sebaceous glands and increased sebum
production which exacerbates plug formation. Scarring is
a potential complication of acne, and can lead to
psychological problems; it may be avoided with early
initiation of treatment.
Benzoyl peroxide is available in a number of formulations
(gels, creams, lotions) and a range of strengths (2.5–10%).
e ecacy of the various strengths, however, does not
appear to dier greatly. Treatment should be applied
sparingly, and started at low concentration to avoid
adverse eects, which include local irritation and
dryness; these eects are usually short-lived (1–2 weeks),
but can lead to non-compliance. is is seen with our
ctional patient Eimear in Workbook 5, as she struggles to
use benzoyl peroxide correctly. Improvement in the
condition is often not seen for several weeks.
8.8.1 Topical treatment of acne
Benzoylperoxide
Topical benzoyl peroxide is eective in mild to moderate
acne against both comedones and inamed lesions. It has
comodolytic, anti-inammatory, and antibacterial
properties. Benzoyl peroxide is lipophilic. It penetrates
the skin to be broken down to benzoic acid and hydrogen
peroxide, generating free radicals which are believed to
have an antibacterial eect by oxidizing proteins in
bacterial membranes. Benzoyl peroxide also has a mild
keratolytic action, causing peeling of the skin.
Table 8.3 Mechanism of action of drugs used to treat acne
Mechanism of
action
Normalizing follicular
keratinization
Decreasing sebum
production
Suppressing bacterial
flora
Preventing
inflammatory response
Benzoyl peroxide Azelaic acid Salicylic acid Retinoids Antibiotics Hormone therapy
Benzoyl peroxide is also available combined with
antibiotics (e.g. clindamycin). Products containing
benzoyl peroxide will bleach clothing and skin that they
come into contact with.
Azelaicacid
Topical application of azelaic acid is eective against both
comedonal and inammatory lesions in mild to moderate
acne, and is particularly useful for the face. It is a carboxylic
acid with signicant antimicrobial activity, as well as
decreasing keratinization within the epidermal layer. It has
been shown to be as eective as oral antibiotics.
198 Chapter 8 Inflammation and the skin: dermatitis, psoriasis, and acne
It should be applied twice daily and continued for several
months; benet is often not seen for up to 4 weeks. It is
less likely to cause local irritation than benzoyl peroxide,
and does not have a bleaching action.
Salicylic acid
Salicylic acid is an eective keratolytic and antibacterial
agent (see Section 8.6.1). Products such as face
washes and creams containing concentrations of 0.5–2%
salicylic acid can help to open up clogged pores and
neutralize the bacteria inside follicles. Salicylic acid is less
eective than benzoyl peroxide and azelaic acid, and is
only used in very mild cases of acne.
Topical retinoids
e mode of action of retinoids is not fully understood
(see above), but in acne their benecial eects include
decreased size and output of sebaceous glands,
antimicrobial eects, and comedolytic action, unclogging
blocked pores. Topical retinoids act synergistically with
topical antibiotics, making this a very useful combination
in treating acne. Topical retinoids for this indication
include tretinoin, its isomer isotretinoin, and the
retinoid-like drug adapalene. ey should be applied
regularly for a minimum of 4 months for optimal benet,
but are not suitable for acne aecting a large area. Redness
and skin peeling often occur initially but reduce with time.
As discussed above (see Sections 8.6.1 and 8.6.2),
retinoids are teratogens and are therefore contraindicated
in pregnancy.
Topical antibiotics
e most commonly used topical antibiotics for acne are
clindamycin and erythromycin. ey are, though, no
more eective than benzoyl peroxide or tretinoin in
treating mild to moderate acne, and their use is
associated with development of antibacterial resistance
to Propionibacterium acnes. Topical antibiotic treatment
should be continued for at least 6 months, but thereafter
no longer than is necessary. Adverse reactions include
local irritation and sensitization; gastrointestinal
disturbance is possible with clindamycin.
8.8.2 Systemic treatment of acne
Oral antibiotics are reserved for moderate to severe
inammatory acne and are more eective than topical
formulations. ose most commonly used are
tetracyclines including tetracycline, oxytetracycline,
and doxycycline. Treatment is long term and may need
to be continued for 2 years or longer; maximum benet
usually occurs at around 4–6 months. Dierent topical
and systemic antibiotics should not be combined as this
increases the risk of development of bacterial resistance.
Patients taking tetracyclines must be careful when out in
the sun as these drugs can precipitate phototoxic
dermatitis. Other more common side eects are
gastrointestinal disturbances such as nausea, vomiting,
and diarrhoea.
Oral retinoids
Isotretinoin is used orally in the treatment of late-onset
acne, which is often unresponsive to systemic antibiotics,
or in severe acne which has not responded to such
treatment. Because of its toxicity, isotretinoin is reserved
for use only under specialist supervision. Side eects
include extreme dryness of skin, nose bleeds, and joint
pains. Isotretinoin, like all retinoids, is a teratogen;
pregnancy must be excluded when initiating, during, and
for several weeks after therapy.
8.8.3 Hormone treatment
Co-cyprindiol is an eective oral treatment for severe
acne in women which has not responded to topical
therapy or oral antibiotics. It combines an anti-androgen,
cyproterone acetate, with ethinylestradiol, a derivative of
17-estradiol, the major endogenous oestrogen in
humans. Cyproterone inhibits the synthesis of
testosterone, as well as blocking the androgen receptor.
e ethinylestradiol component of co-cyprindiol
suppresses ovarian androgen production, and increases
levels of sex hormone binding protein, which in turn
reduces the amount of free testosterone circulating. It also
blocks the conversion of testosterone to
dihydrotestosterone, the most potent and active
androgen in skin. As sebum production is mediated by
androgen, these eects combine to reduce the output
from sebaceous glands. Co-cyprindiol is an eective
treatment of hirsutism in women, as hair growth is also
androgen-dependent. It is an ideal treatment for women
with acne or hirsutism who also require contraception,
but is not prescribed solely for contraceptive purposes. In
Workbook 5, Eimear’s troubling acne is nally resolved
when she takes co-cyprindiol.
e most common side eects of co-cyprindiol are
menstrual irregularities, breast tenderness, nausea,
8.9 Other dermatological conditions 199
vomiting, and headache. It should be avoided where there
is a risk of venous thromboembolism (see Chapter 4).
Combined oral contraceptives (see Chapter 15,
Section 15.4.3) are also eective in the treatment of acne,
acting largely through suppression of ovarian androgen
synthesis to decrease sebum production. (Progestogenonly contraceptives should be avoided as they may worsen
the condition.) Combined oral contraceptives are
associated with an increased risk of thrombosis, although
this is less than with co-cyprindiol.
Corticosteroid use in acne
Although corticosteroids can worsen acne, they are
occasionally used in extremely severe and resistant cases.
Injections of triamcinolone (a synthetic steroid) directly
into the lesions, or a short oral course of a corticosteroid,
have been shown to be eective in providing rapid
improvement. Topical corticosteroids are not very
eective, although they are sometimes used in
combination with isotretinoin in severe
inammatory acne.
8.9 Other dermatological conditions
A number of other conditions can aect the skin,
including fungal, parasitic, viral, and bacterial (cellulitis)
infections, and alopecia.
Table 8.4 Other skin conditions and drugs commonly used to treat them
Dermatological condition Examples of drugs used Action Adverse effects
Fungal infections
Dermatophytoses
(ringworm/tinea infection)
Pityriasis versicolor
(scaliness and discoloration of
the skin)
Candidiasis (thrush) Terbinafine; topical
Angular cheilitis
(cracking or soreness at corners
of the mouth)
Bacterial infection
Cellulitis
(infection of the dermal and
subcutaneous layers of the skin)
Erysipelas (superficial infection
of the skin)
Infected burn wounds Silver sulfadiazine
Simple impetigo (highly
contagious superficial infection
of the skin)
Long-standing or extensive
impetigo
Topical imidazoles (e.g.
clotrimazole, ketoconazole,
miconazole); griseofulvin;
terbinafine; amorolfine;
undecenoates; compound
benzoic acid; tolnaftate
Shampoo containing
ketoconazole or selenium;
topical imidazoles
imidazoles; nystatin
Miconazole and nystatin
ointments
Oral broad-range antibiotic
(e.g. flucloxacillin or
clarithromycin)
Oral antibiotic
Topical fusidic acid,
polymyxins, neomycin (or
mupirocin if MRSA)
Antiseptic detergents, e.g.
povidone–iodine
Oral flucloxacillin,
clarithromycin, or
erythromycin
e drugs used to combat these conditions, and their adverse
reactions, are summarized in Table 8.4. (See Chapter 22 for
more details of antifungal and anti-infective agents.)
Kill or inhibit growth of fungi Contact dermatitis
Rash
Irritation of the skin: burning,
itching, dryness, stinging, and
redness
Kill or inhibit the growth of
bacteria
Softens crusts
200 Chapter 8 Inflammation and the skin: dermatitis, psoriasis, and acne
Table 8.4 (Continued)
Dermatological condition Examples of drugs used Action Adverse effects
Rosacea (enlargement of facial
blood vessels giving pronounced
flushed appearance, papules and
pustules)
Simple Topical metronidazole or
azelaic acid
Moderate or severe Oral antibiotics, e.g.
tetracycline or erythromycin
Viral infections
Herpes simplex, herpes labialis
(cold sores)
Parasite infections
Scabies Permethrin, malathion, benzyl
Head lice Dimeticone, carbaryl,
Crab lice Carbaryl, malathion,
Aciclovir, penciclovir,
idoxuridine
benzoate (not in children)
malathion, phenothrin
phenothrin
Inhibit growth of virus
Neurotoxic to parasites
through different mechanisms
to cause paralysis: e.g.
carbaryl and malathion are
AChE inhibitors; permethrin
and phenothrin bind to Na
channels and prevent them
from closing
+
Contact dermatitis
Skin irritation
Rashes
Oedema
Hypersensitivity reaction
Respiratory allergy reaction
AChE, acetylcholinesterase; MRSA, methicillin-resistant Staphylococcus aureus
Key references and suggested reading
Haider A, Shaw JC. Treatment of acne vulgaris. JAMA 2004; 292:
726–35.
Hengge UR, Ruzicka T, Schwartz RA , Cork MJ. Adverse eects of
topical glucocorticosteroids. J Am Acad Dermatol 2006; 54:
1–15.
NICE. Management of atopic eczema in children from birth up
to the age of 12 years: National Institute for Health and Care
Excellence Clinical guidelines CG57, 2007. http://guidance.
nice.org.uk/CG57.
Tucker R, Walton S. e role of benzoyl peroxide in the
management of acne vulgaris. Pharm J 2007; 279: 48–53.
Wintereld LS, Menter A, Gordon K, Gottlieb A. Psoriasis
treatment: current and emerging directed therapies. Ann
Rheum Dis 2005; 64: ii87–90.
SUMMARY OF DRUGS USED FOR ECZEMA (DERMATITIS), ACNE, AND PSORIASIS
8.9 Other dermatological conditions 201
Therapeutic
Drugs/vehicle Mechanism of action Common clinical
class
Emollients Ointment 1) Moisturizers hydrate roughened
Creams Daytime use in eczema, easy to
Lotion Cooling
Gel Cooling
Bath/shower oils Trap water under film of oil,
Soap substitutes (emollient
cleansers)
Topical
corticosteroids
Topical
calcineurin
inhibitors
Vitamin D
analogues
Dithranol Dithranol Inhibits keratinocyte proliferation
Examples include:
Hydrocortisone
Fluocinolone
Betamethasone
Clobetasone
Clobetasol
Tacrolimus
Pimecrolimus
Calcitriol (dihydroxy-vitamin
D3)
Calcipotriol
Tacalcitol
skin surface to restore skin barrier
against allergens and irritants, and
to reduce itching
2) Humectants attract and retain
water within the stratum corneum
Enter nucleus of cells to alter gene
expression, leading to overall
dampening down of inflammatory
response
Prevent transcription of proinflammatory genes to dampen
down immune response
Activate vitamin D receptors to alter
gene transcription
Suppress keratinocyte proliferation
and the inflammatory response
(mechanism not fully understood).
uses
Comments Common adverse drug
Dermatitis
Psoriasis
Eczema
Psoriasis
Extremely resistant acne
Atopic dermatitis Used short term for patients over 2,
Long-term treatment of
mild to moderate
psoriasis
Mild to moderate
psoriasis (discrete
plaques)
Suitable for dry thickened skin but
not for weeping eczema
apply
Commonly contain preservatives that
could irritate
Require frequent application
Used for weeping eczema and for
hairy areas
Suitable for face and scalp
preventing skin from drying out
Aqueous cream or emulsifying
ointment
Use on wet skin
Added to emollients when their
sustained and correct use has
proved ineffective
Use lowest strength possible, and
apply thinly, 1–2 times daily
when emollients and topical steroids
are ineffective
Can take up to 6 weeks to take effect Local skin irritation, e.g. burning,
Start with low concentration (e.g.
0.1%) and build up gradually if
tolerated to 3%
reactions
Sensitization
Localized skin thinning
Infection
Systemic steroid effects for
potent steroids
Local irritation
Burning sensation
Itch
Erythema (skin reddening)
Skin infections
itching
Acute inflammation
Stains skin and clothing yellow