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Chapter 8
Inflammation and the skin:
dermatitis, psoriasis, and acne
Useful terms for this topic
Atopy: A genetic disposition to hypersensitivity or
allergic states, characterized by high IgE antibody
levels.
Eczema/dermatitis: Inammatory condition of the
skin. Terms are often used interchangeably, although
eczema is sometimes reserved for atopic dermatitis.
Emollient: Substance that moisturizes the skin.
Epidermis: Outer layer of the skin.
Langerhans cells: Specialized cells in the epidermis
that engulf foreign pathogens, and then process and
present them to cells of the immune system to initiate
the inammatory response.
Keratinocytes: Main cell type in the epidermis.
Contains keratin, a brous protein which gives
strength to the epidermis.
Pruritus: Itching.
Vehicle: The bulk phase which carries the drug.
Skin conditions, such as those covered in this chapter,
account for between 10% and 20% of consultations in
general practice in the UK. As well as causing much
discomfort, they can have a signicant psychological
impact on the patient, particularly when aecting
visible areas such as the face or hands. Some of these
disorders are associated with particular phases in our
lives, for instance acne, which aects up to 90% of
teenagers, and can lead to acute embarrassment and
social isolation.
Elvis, our ctional patient in Workbook 5, like many
suerers of dermatitis, or inammation of the skin, has an
inherited disposition to developing classic allergic
diseases. Such individuals are described as atopic and
may be aected by the related conditions, asthma and
allergic rhinitis. Elvis suered dermatitis as a baby and
asthma as a young child, and, as we shall see, as a
teenager he is again aected by atopic dermatitis. (Atopic
dermatitis is frequently referred to as eczema, although
this term is often used interchangeably with dermatitis,
describing all such inammatory conditions of the skin,
irrespective of the trigger, see Section 8.3.)
In this chapter, and the workbook that follows, we
consider the underlying pathology, symptoms, and
treatment of three common skin conditions: dermatitis,
psoriasis, and acne. First, though, we must look at the
skin’s structure and physiology, an understanding of
which will guide the eective management of these
conditions. Of particular signicance to the treatment of
skin conditions is the pharmaceutical formulation of
topically applied drugs. Some agents are available in a
range of dierent preparations, the suitability of which
will need to be determined on an individual basis,
depending on symptoms. ese aspects of medication
applied topically to the skin are also explored in the
current chapter.
184 Chapter 8 Inflammation and the skin: dermatitis, psoriasis, and acne
Dermal papillae
Hair
Pore
8.1 Structure and physiology of the skin
e skin is the body’s largest organ, constituting about
16% of body weight. Its main functions are:
• protection against heat, light, injury and
infection
• regulation of body temperature
• retention of water
• biochemical synthesis (e.g. vitamin D)
• sensory detection.
e skin has three main layers: the outermost epidermis,
the dermis, and the deeper subcutaneous, or hypodermis
(Figure 8.1). e composition of these layers is described
in more detail in Box 8.1. e epidermal layer is largely
composed of specialized cells called keratinocytes,
and constantly renews itself as cells migrate from the
basal cell layer, where they are formed, to eventually
slough o at the surface. As they make this journey the
characteristics of keratinocytes change; their keratin
content increases and they lose intracellular organelles.
e thickness of the skin is determined by the depth of
the epidermal layer, and varies around the body; for
instance, it is much thicker on the palms of the hands
and soles of the feet. is is of importance for the
absorption of topically applied drugs into the circulation,
which is signicantly greater where skin is thin,
increasing the risk of adverse eects. In addition to
keratinocytes, the epidermis contains two other
important cell types.
1. Melanocytes are responsible for secreting the pigment
melanin, which determines the skin’s coloration.
2. Langerhans cells, or dendritic cells, are part of the
immune system and engulf invading foreign material.
ese cells act as antigen presenting cells, processing
parts of the pathogen, which they present on their
surface to lymphocytes at local lymph nodes, thereby
initiating the immune response. ey are central to the
development of eczema/dermatitis.
Epidermis
Dermis
Subcutaneous
layer
Arrector pili
muscle
Sebaceous gland
Figure 8.1 The structure of the skin.
The layers of the skin and associated structures, including a hair follicle with a sebaceous gland.
Sweat gland
Cold receptor
Heat receptor
Blood
vessel
Connective
tissue
Nerve
Fat lobules
8.1 Structure and physiology of the skin 185
Keratinocyte migration
Box 8.1
Layers of the skin
1. The epidermis
e epidermis or outer layer of the skin acts as a
protective barrier, and is composed mainly of
keratinocytes. It is made up of distinct sublayers
through which cells migrate (see Figure a). As they
make this journey, the cells undergo keratinization, a
process in which they express increasing amounts of
the brous protein keratin. is protein forms thick
cable-like structures connecting cells together, and
lending strength to the epidermis.
Stratum basale (stratum germinativium) Immature
keratinocytes are formed in the division of columnshaped stem cells in this, the deepest layer of the
epidermis.
Stratum spinosum e migrating cells begin the
process of keratinization; the keratin bres give the
cytoplasm a spiny, or prickly, appearance. is layer is
deeper where skin is thick.
Stratum granulosum Keratinocytes take on a
polyhedral shape, with a more granular cytoplasm
and increased amounts of keratin. ey begin to
atten and to lose intracellular organelles, such as the
nucleus. is layer is three to ve cells thick.
Stratum lucidum is is found only in regions where
the skin is particularly thick, such as the soles of the
feet, and is made up of dead cells. It serves to reduce
friction and shear forces between the stratum
granulosum and the stratum corneum.
Stratum corneum e cells in this layer have a full
complement of keratin, and have lost organelles.
ese mature keratinocytes are attached together
laterally, providing strength. ey are attened, and
the outermost cells are dead and are shed at the
surface. e layer can be between three and twenty
cells deep, depending on the skin’s thickness. e
stratum corneum allows absorption of water to keep
the skin hydrated.
e migration of keratinocytes, starting at the
stratum basale and ending as they are sloughed o at
the skin’s surface, normally takes about a month. is
is accelerated in psoriasis (see below).
and maturation
Dead keratinocytes at surface
slough off, replaced by cells
Stratum
corneum
Stratum
lucidum
Stratum
granulosum
Stratum
spinosum
Stratum
basale
Stratum corneum
Stratum
lucidum
Stratum
granulosum
Stratum
spinosum
Stratum
basale
Dermis
from beneath.
Mature keratinocytes with
keratin cables making up
~85% of protein content.
Cells are attened and
anuclear.
Maturing cells migrate to
surface, attening and
losing organelles. Increased
keratin content forms
strong cable structures.
Stem cells divide to form
immature keratinocytes—
keratin makes up about
30% of their protein.
Figure a The layers of the epidermis.
The arrows indicate the migration of keratinocytes, continuously being formed in the stratum basale, to the
surface of the skin, where in mature form they make up the majority of the stratum corneum.
Adapted from Gray H, Anatomy of the Human Body (20th edn), 1918. Philadelphia: Lea & Febiger.
186 Chapter 8 Inflammation and the skin: dermatitis, psoriasis, and acne
Box 8.1 Layers of the skin
2. The dermis
e much thicker dermis, beneath the epidermis, is
composed mainly of connective tissue, and imparts
pliability and protection from mechanical injury. It is
also the site of vitamin D synthesis. Its rich vascular
network supplies nutrients and oxygen to the
epidermal layer, which lacks blood vessels. Additional
structures include:
• sweat and sebaceous glands (see below)
• hair follicles—downward growths of the epidermis
which produce hair, involved in temperature
regulation; when the body gets cold, the associated
arrector pili muscle contracts and the hair stands
up, helping to reduce heat loss
• local lymph nodes
• nerve bres and free nerve endings responsible for
sensing temperature change, pain, and itchiness
• receptors for touch, pressure, and vibration.
e glands of the skin are located in the dermis,
secreting product through the epidermis to the
surface. ey comprise two main types, sweat and
sebaceous glands.
e sweat glands can be divided into three groups.
1. Eccrine glands produce a thin watery sweat,
secreted on to the skin’s surface to promote heat
loss through evaporation. ey are the most
common sweat glands, and are particularly
abundant in thick skin such as on the palms of the
hands and soles of the feet, as well as the forehead.
Secretion is stimulated by changes in body
temperature and by emotional stimuli, such as
stress, anxiety, and pain. e innervating
sympathetic neurons are unusual in that they
release acetylcholine, not noradrenaline, and this
acts at M3 receptors. Activation of these receptors
accounts for the unwanted sweating associated
with the use of some medications, such as the
muscarinic agonist bethanacol used for urinary
retention. Similarly, drugs with antimuscarinic
action, for instance atropine and hyoscine,
commonly cause dry skin.
2. Apocrine glands open into the upper portion of a
hair follicle rather than directly onto the skin’s
surface. ey have a more limited distribution and
are primarily located in the armpits. e secretion
produced is thicker, and is rich in proteins and lipids
which undergo decomposition by bacteria,
generating products with strong odours. Eccrine
glands express adrenoceptors rather than cholinergic
receptors, and increased secretion occurs in
response to emotional stimuli, such as stress, anxiety,
and pain. ese glands are inactive until puberty
when hormonal changes lead to their stimulation.
3. Apoeccrine glands have characteristics of both
eccrine and apocrine glands. ey have been
identied in more hairy regions, such as armpits,
and are known to appear during puberty, although
their function is as yet unclear.
e sebaceous glands are intimately associated with
hair follicles (see Figure 8.1). ey secrete oily sebum
which acts as a natural moisturizer. ey are under
hormonal control, with secretions also increasing at
puberty; overactivity of these glands underlies the
development of acne (see Section 8.7).
3. The subcutaneous layer
Also called the subcutis, or hypodermis, this layer is
made up of adipose and connective tissue. It acts as a
protective cushion and is involved in temperature
regulation by providing insulation.
8.2 Medication for topical application to the skin
e prevalence of some of the more common diseases
aecting the skin is set out in Table 8.1. Treatment of
these disorders aims not only to alleviate the underlying
cause of the damage, but also to restore the skin’s normal
function. With respect to the latter,
pharmacologically inert agents, e.g. emollients, play a
central and crucial role, restoring the appearance and
integrity of the skin, and reducing symptoms such as
itching. Drugs used in the treatment of skin conditions
are often available in a number of forms; selecting the
8.3 Eczema/dermatitis 187
Table 8.1 Prevalence of common skin conditions and the sites most often affected
Clinical diseases Common locations Prevalence (%)
Dermatitis and eczema Seborrhoeic dermatitis: scalp, face, and ears 10
Dermatitis: neck and elbows 7–30
Acne Face, chest, upper back, and arms 22–33 (80–90 in teenagers)
Psoriasis Head, ears, and elbows 1–3
Viral warts Hands and feet 1–16
Skin cancer Exposed skin 0.3
Fungal and bacterial infections Anywhere 10–20
most appropriate preparation must take into account not
only the type of skin condition, but also the nature of the
symptoms.
8.2.1 Vehicles used in topical preparations
Preparations of drugs to be applied topically to the skin
usually consist of the active ingredient mixed in a bulk
phase, or vehicle. Drugs may be available in dierent
vehicles, and so choice of product will be determined by
suitability for the particular skin disorder, as well as the
symptoms present. For example, ointments are generally
better for the treatment of dry skin conditions, as they aid
rehydration. e properties and uses of dierent vehicles
are explored further in Box 8.2. Choice of vehicle should
also take into account patient preference, as this will
inuence compliance.
8.2.2 Factors influencing the absorption of
drugs from topical preparations
In the treatment of skin diseases the aim is to largely
restrict delivery of drug to the skin, avoiding absorption
into the systemic circulation. Sometimes, though, the skin
is used as a route of administration of systemically acting
drugs. In this case, the rate and extent of absorption of a
drug applied topically to the skin is determined by a
number of factors.
1. Characteristics of the drug, such as water solubility
and molecular weight; low molecular weight drugs
(e.g. <600 Da) are better absorbed than larger
molecules.
2. e vehicle used (see comments in Box 8.2).
3. Skin thickness, with more drug being absorbed from
thin skin (e.g. scalp and face) than from thick skin (e.g.
palms and soles of the feet).
4. Skin hydration, e.g. vehicles with an ointment or
emulsion (especially water-in-oil) base increase
hydration. Applying to hydrated skin after a bath also
increases absorption.
5. Skin condition, as damaged skin (e.g. in burns or
psoriasis) will allow greater absorption.
8.3 Eczema/dermatitis
e terms eczema and dermatitis are often used
interchangeably to describe a chronic inammation of
the epidermis and dermis that is accompanied by
pruritus (itching) and localized oedema of the epidermis,
creating a swollen patch of skin, called spongiosis. Other
features include redness, dry skin, which is often
thickened in the areas that have been rubbed or
scratched, red lumps or blisters, weeping lesions, or
crusty deposits (Figure 8.2). Excessively dry and
thickened skin is described as lichenied.
Dermatitis is often subdivided, based on the causal factor,
or irritant.
• Atopic dermatitis is the most prevalent form, and is
also the most common skin condition in children,
aecting 10–20%, most usually with an onset before the
age of 5. (e term eczema is sometimes reserved for
atopic dermatitis.) e areas of aected skin are
commonly on the inside of the elbows and backs of the
knees (exures). Atopy refers to the genetic disposition
to hypersensitivity or allergic states, characterized by
188 Chapter 8 Inflammation and the skin: dermatitis, psoriasis, and acne
Box 8.2
Choice of vehicle in the treatment of skin conditions
In treating skin conditions, both the active drug and
the vehicle it is delivered in are important. e choice
of vehicle depends on a number of
factors (Table B8.2). Its characteristics will aect the
degree of rehydration of the skin, and therefore also
penetration of the drug; it may also have an anti-
Table B8.2 Properties and uses of vehicles for skin conditions
Vehicle Physical and chemical
Ointment Water miscible; can be washed off Lubricates, e.g. in burn dressings
Creams Oil-in-water; washable Well absorbed
Paste Stiff preparation of finely powdered
Powder Drying and cooling
Gels Semi-solid preparations, usually
Lotions Suspensions of powder in water, or
a
Intertriginous areas: where two surfaces of the skin are normally in contact, such as between fingers and toes, armpits.
properties
Water immiscible; not easily
washed off
Water-in-oil; acts similarly to
ointments; less greasy than
ointments, but more greasy than
oil-in-water creams
solid, suspended in ointment
Very adhesive
Reduces friction between opposing
skin surfaces
Absorbs moisture and creates
increased area for evaporation
aqueous
Clear and quick drying
No residue
dilute emulsion of oil-in-water
Characteristics and uses Examples
Aids penetration of drugs
Chronic dry skin conditions
Messy
Cosmetically acceptable, easy to apply
Vehicle for water-soluble drugs
Suitable for moist or weeping lesions
Increases skin hydration
Vehicle for fat-soluble drugs
Able to absorb discharge (e.g. pus)
Protects inflamed, lichenified, and
damaged skin
Intertriginousa areas and chronically
damp areas (e.g. feet and under nappy)
Useful in hairy areas or where residue is
unacceptable (e.g. face)
Superficial oozing dermatoses
Intertriginousa areas, inflammation and
tenderness (e.g. sunburn, acute contact
dermatitis)
inammatory eect. Cosmetic factors must also be
considered. For example, creams may be more
suitable for daytime use because they are lighter,
cosmetically more acceptable, and easier to apply
than greasier ointments, which may be reserved for
use at night.
Macrogels and PEG mixtures
Emulsifying ointment
White soft paraffin
Paraffin-based ointments
Aqueous cream BP
Cetomacrogol cream
Oily cream BP
Zinc cream
Zinc oxide pastes
Talcum powder
Antifungal powders
Polymers and copolymers
Calamine lotion
high IgE antibody levels. Approximately half of children
with atopic dermatitis will go on to develop other atopic
conditions, such as allergic rhinitis and asthma (the
‘atopic triad’; see Chapters 10 and 11). Langerhans
cells, specialized immune cells in the epidermis, detect
and capture pathogens pervading the skin barrier, and
play a central role in the development of atopic
dermatitis. ey migrate to local lymph nodes and
8.4 Treatment of dermatitis 189
Figure 8.2 Appearance of skin affected by dermatitis.
(A) Reddened and inflamed skin at wrists. (B) Classic appearance of contact dermatitis.
(A) From Saxe N, Jessop S, Todd G, Handbook of Dermatology for Primary Care (2nd edn), 2007. By permission of Oxford University Press. (B) ©
DermNetNZ.
present the antigen/allergen to lymphocytes, thereby
initiating typical 2-mediated immune responses with
antibody generation as a central feature (see Figure
P3.2 in the Introduction to Part 3). Pruritus is the most
common symptom of atopic dermatitis, often
preceding the appearance of a rash. Open lesions may
follow spontaneously, but more usually result from
scratching. A number of factors can aggravate atopic
dermatitis, including temperature extremes, irritants
such as bubble bath, food, or inhaled allergens, or
stress. Acute are-ups often result from invasive
bacterial or viral infection. Approximately 60% of
aected children are symptom free by the age of 16.
• Allergic contact dermatitis is a hypersensitivity
reaction resulting from contact with an allergen to
which the individual has previously been sensitized,
such as latex or nickel.
8.4 Treatment of dermatitis
e strategy for management of dermatitis should include
both avoidance of triggers, where these have been
identied, and medication. Here we focus on treatment
involving emollients and two classes of drugs
(corticosteroids and calcineurin inhibitors).
Antihistamines may also be useful to ease symptoms such
as itching (see Chapter 10, Section 10.2.1). A non-sedating
antihistamine is usually preferred, but where symptoms
interfere with sleep, one with sedative action may be
chosen.
• Irritant contact dermatitis can follow contact with
irritants such as detergents, cleaning agents, plastics,
etc. ere is no immunological basis to this form of
dermatitis.
• Photoallergic/phototoxic dermatitis is due to
conversion of chemicals into allergens or toxins in the
skin when exposed to UV light.
• Seborrhoeic dermatitis aects areas of the skin rich in
sebaceous glands, most commonly the scalp, and areas
of the face such as around the nose, between the
eyebrows, and behind the ears. Babies’ scalps are often
aected (cradle cap). Skin rst appears red and aky,
with greasy patches and yellow scales developing. e
condition often results from overgrowth of the yeast
Pityosporum ovale. Treatment typically involves
antifungal agents.
8.4.1 Emollients
In dermatitis the integrity of the skin is compromised as a
result of both the inammatory process itself, and
damage inicted by scratching. Emollients, creams, and
ointments which hydrate and soothe the skin are rst-line
treatment for dermatitis. e aim is to adequately
rehydrate the stratum corneum and restore the skin’s
barrier function, protecting against allergens and
irritants. is will also reduce itching.
190 Chapter 8 Inflammation and the skin: dermatitis, psoriasis, and acne
A variety of emollients are available, ranging from light
aqueous creams, which are cosmetically more
acceptable, to the more occlusive,1 but greasier and
messier, ointments. Some preparations contain urea and
propylene glycol to improve penetration by loosening the
keratinocyte layer, while others contain humectants that
attract and retain water, such as glycerin. Application
frequency varies with type; creams require more frequent
application than ointments.
Emollients should be applied liberally, making issues
such as appearance on the skin, smell, eect on clothing,
and ease of removal important in the choice of
preparation. ey are often under-used, and patients may
need counselling to ensure that sucient quantities are
applied regularly, thereby reducing the likely need for
topical corticosteroids.
8.4.2 Corticosteroids
When emollients are insucient to manage dermatitis,
topical preparations of corticosteroids are extremely
useful agents.
Mechanism of action
concentration present, and product choice will depend on
the severity of the skin disease, as well as the site aected.
Potent and very potent steroids should be avoided on
delicate thin skin, such as on the face or genitals. Where a
steroid is available in more than one type of preparation,
the choice of product may also need to take into account
the vehicle’s suitability for the symptoms (see Box 8.2
for the signicance of dierent vehicles).
Key principles for the use of topical corticosteroids
A number of points are worth noting to guide the correct
use of corticosteroids in order to gain maximum benet,
whilst minimizing the risk of unwanted eects.
• Use only when sustained and correct use of emollients
has proved ineective. When introduced they should
be used alongside emollients (see next point).
• Apply to hydrated skin (e.g. after bathing, or after use of
an emollient) for maximum penetration and eect.
• Apply thinly to aected area only, and no more
frequently than twice daily.
• Use the least potent formulation possible, and for as
short a time as possible (usually no more than 2 weeks).
Corticosteroids are anti-inammatory agents which enter
cells and bind to intracellular receptors (see Chapter 2,
Section 2.2.6). e receptor–steroid complex acts within
the nucleus to change gene expression, suppressing proinammatory genes and inducing expression of antiinammatory genes (see Chapter 9, Section 9.3.2 and
Box 9.2, for more details of the mechanism of action of
corticosteroids). e overall eect is a dampening down
of the processes underlying dermatitis (see Box 8.3). As a
consequence of their mode of action, the therapeutic
response is slow to develop, requiring regular application
over a sustained period.
Corticosteroids can provide long-term relief, but do not
oer a cure; for example, the tendency of an atopic
individual to develop dermatitis will not be modied, and
when treatment is halted, symptoms may well recur.
Differences in steroid preparations
Topical corticosteroids are classied according to potency,
or strength, into four main groups (Table 8.2). Potency
depends on the nature of the steroid together with the
1 Occlusive here means a preparation which, when applied to the skin,
acts as a physical barrier. is is achieved by thick and greasy
preparations.
• Use low- or medium-strength preparations where long-
term treatment is necessary.
• Use low-strength steroids where the skin is thin (e.g.
face), to avoid excessive absorption and the increased
risk of side eects.
Side effects of topical steroids
With careful use systemic effects from topical
corticosteroids can be avoided, even with high potency
preparations. Local adverse effects are more common,
particularly at the site of application of the stronger
agents. The local suppression of the immune response
may lead to infection, thinning of the skin, striae
(stretch-mark-like damage), and telangiectasia (visible
dilated blood vessels). Topical corticosteroids have
also been known to precipitate acne. Rebound effects,
with enhanced symptoms of the underlying skin
condition when treatment is stopped, are also of
concern.
A short course of an oral corticosteroid such as
prednisolone may be justied to control severe acute
eczema. Owing to the risk of side eects (see above), such
treatment does not feature in the long-term management
of the condition.
8.4 Treatment of dermatitis 191
Box 8.3
Development and treatment of atopic dermatitis
Damaged stratum corneum
Penetration of antigen
Helper
T-cell
Th2
cell
↑ Antigen-specic IgE
↑ Mediators of inammation↑ Pro-inammatory
cytokines
Inammation, itching, discomfort,
weeping.
Decient epidermal barrier
water loss dehydration
itching and scratching
APC
B-cell
+ve feedback
Mast cell
activation
Figure b A scheme for the development and perpetuation of atopic
dermatitis.
Figure b provides a simplified illustration of how damaged epidermis, infiltration by
antigens, and the inflammatory response contribute to the symptoms of atopic
dermatitis, and give rise to a pattern of self-perpetuating feedback.
Treatment of atopic dermatitis targets dierent
aspects of the disease process.
Emollients restore the condition of the epidermis,
rehydrating it to establish an eective barrier to water
loss, and reducing penetration of allergens and
irritants. Itching is reduced and the skin’s appearance
becomes more normal.
Corticosteroids alter gene expression to increase the
levels of anti-inammatory proteins, and decrease
pro-inammatory proteins. e result is a dampening