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202 Chapter 8 Inflammation and the skin: dermatitis, psoriasis, and acne
Therapeutic
Drugs/vehicle Mechanism of action Common clinical
class
Tars Complex mixtures of
Topical salicylic
acid
Retinoids Topical:
Methotrexate Methotrexate Anti-proliferative
Immuno-
suppressants
Biological agents Etanercept
Topical
antimicrobials
organic constituents
Salicylic acid Antibacterial and keratolytic (peeling
adapalene
isotretinoin
tazarotene
tretinoin
Oral:
acitretin
isotretinoin
Ciclosporin Inhibits calcineurin to block immune
Infliximab
Adalimumab
Ustekinumab
Secukinumab
Benzoyl peroxide 1. Broken down to benzoic acid and
Azelaic acid Decreases follicular keratinization,
Inhibit proliferation and inflammation
in epidermal layer (mechanism not
clear)
agent)
Comedolytic effect by opening
plugged follicles
Mechanism of action not fully
understood. Leads to:
1) Reduction in keratinocyte
differentiation and proliferation
2) Reduction in size and output of
sebaceous glands
3) Anti-inflammatory effects
4) Anti-microbial effects
Inhibits dihydrofolate reductase,
blocking folate biosynthesis
necessary for DNA synthesis
response
Monoclonal antibodies directed
against the pro-inflammatory
cytokine TNF-
Monoclonal antibodies directed
against pro-inflammatory interleukins
hydrogen peroxide; free radicals
generated have antibacterial effect
2. Keratinolytic
and antibacterial
uses
Mild to moderate
psoriasis
Dermatitis
Scalp psoriasis
Mild acne
Psoriasis
Severe acne
Moderate to severe
psoriasis
Severe unresponsive
psoriasis
Severe disabling psoriasis Third-line use only Infection, e.g. tuberculosis and
Mild to moderate acne Start with low concentration and
Mild to moderate acne
Rosacea
Messy to use Local irritation
Risk of salicylate toxicity with
widespread use, or in babies
(symptoms include confusion,
dizziness, headache)
Avoid in pregnancy
Increased sensitivity of skin to
sunlight
Administered once weekly Infection
Normally used once weekly Nephrotoxicity
gradually increase
Improvement only seen after 4 weeks Local irritation
reactions
Acne-like lesions
Photosensitivity
Stains
Sensitivity
Local irritation
Ulceration
Teratogenicity
Severe dryness of skin
Erythema (skin reddening)
Peeling
Irritation
Burning
GI bleeding
See also Chapter 22
Hypertension
See Chapter 9
hepatitis B
Nausea
Abdominal pain
Injection site reactions
Skin irritation, dryness, and
peeling
Pruritus
Skin discoloration
Comments Common adverse drug
Antibiotics:
Topical
Oral Tetracycline
Hormone
treatment
Erythromycin
Clindamycin
Oxytetracycline
Erythromycin
Co-cyprindiol
(ethinylestradiol and
cyproterone)
Combined hormonal
contraceptives
Kill or inhibit growth of bacteria Moderate to severe acne Long-term use required Local irritation
Severe acne GI disturbance
Anti-androgen effects lead to
decreased sebum production
In women only:
Severe acne
Hirsutism
Contraception
Useful where contraception also
required
Sensitization
GI disturbance (clindamycin)
Nausea
Vomiting
Abdominal cramps
Liver toxicity
Fluid retention
Thrombosis
Weight gain
8.9 Other dermatological conditions 203
WORKBOOK 5
Dermatology: atopic dermatitis, acne,
and psoriasis
Three cases of chronic skin diseases and their management
Patient 1, Elvis: a simplified case history
Sunita has taken Elvis, one of her triplets, to yet another GP appointment. Elvis has again had a
sleepless night, scratching his neck and body so fiercely that he has drawn blood.
A table of clinical clerking abbreviations is given on page xviii.
SUMMARY OF CLINICAL CLERKING FOR ELVIS KAISER AT GP
SURGERY
Age: 13 years
PC: Itchy red and swollen areas at the back of neck, inside of elbows, and trunk. Inside of elbows is
painful and weeping.
HPC: The itching started 6 months ago and has become progressively worse. Different emollients have
been used as prescribed. They provided some relief, but overall there has been no improvement.
1 Symptoms of acute dermatitis:
• skin—itchy,red,hot,dryandscaly,butcanbewetandweeping,andswollen
• bacterialinfectionmaybepresent.
2 Symptoms of chronic dermatitis:
• skin—dryandthickened,butcanbescalyorcrackedasaresultofcontinualscratching.
Any area of the skin can be affected, but most commonly it is the inside of elbows, wrists, backs of
knees, and around the neck.
PMH: Atopic dermatitis (eczema) from 1 month until 3 years. Asthma from 1 year until 4 years.
The most common type of dermatitis, atopic dermatitis, is linked to hay fever and asthma (called
the ‘atopic triad’). Atopic individuals have an inherited disposition to hypersensitive (or allergic)
states, characterized by high immunoglobulin E (IgE) antibodies.
Atopic dermatitis affects 10–20% of children of school age in the UK. It clears up in approximately
60% by the age of 16.
DH:
1) Light liquid paraffin bath additive
WORKBOOK 5 Dermatology: atopic dermatitis, acne, and psoriasis 205
2) Emollient soap substitute
3) Emollient cream
4) Hydrocortisone cream, 0.1%
The bath additive, soap substitute, and emollient cream all act as moisturizers. They are often
under-used, and should be chosen in consultation with the patient to improve compliance.
Hydrocortisone cream (0.1%) is a mild potency corticosteroid. Together they form the cornerstone
of treatment for dermatitis: emollients for routine use and corticosteroids to manage flare-ups.
FH: His grandfather and brother both have asthma. His brother suffers from hay fever.
Genetic factors are important in dermatitis. These inherited factors make patients more sensitive
to allergens in the environment and increase the risk of developing the condition. Other factors
which can aggravate atopic dermatitis are:
• allergens(e.g.food,contact,orinhaled)
• extremesoftemperature
• secondaryinfection(usuallyStaphylococcusaureus)
• irritantsinsoapsanddetergents
• hormonalchangesinwomen(causedbythemenstrualcycleorpregnancy).
O/E: Oozing and crusted lesions on inside of elbow. Dry, thickened, and scaly skin all over back, neck,
and backs of knees.
The elbow lesion may be infected; the other observations are consistent with chronic dermatitis.
However, symptoms are similar to those caused by the contagious disease scabies, which should be
excluded. Patients should be asked if other members of the household have the same symptoms.
O/Q: A general approach to a patient with dermatological symptoms should begin by evaluating the
answers to the following questions.
1) When did the itching start, and for how long has it persisted?
2) Which factors make it worse?
3) Have the lesions recently changed in size, appearance, or severity?
4) What types of lesions are present, and how are they distributed?
Many types of lesion have a characteristic distribution or pattern. The consistency, borders, and
colour of the lesions are all important.
5) Where are they located?
Specific conditions will almost always affect certain locations. Atopic dermatitis, for example, most
commonly affects the insides of elbows and backs of knees. Lesions involving the eye, mouth,
genitalia, and rectal areas should be referred immediately for specialist attention.
6) What is the patient’s medical or dermatological history?
Pre-existing conditions may aid assessment. Elvis’s history of asthma and dermatitis indicates
atopy and therefore likelihood of recurrence. Certain diseases, e.g. diabetes, cancer, and alcoholism,
could predispose to dermatological conditions, as can self-neglect.
7) What medications have been used in the past?
A previously ineffective medication should not be used, although whether it was used correctly
must be established.
206 Chapter 8 Inflammation and the skin: dermatitis, psoriasis, and acne
Diagnosis: Infected chronic atopic dermatitis
Plan: Continue use of emollients and add:
• betamethasone valerate (0.1%) twice daily for 7 days, and thereafter for flare-ups
• mupirocin cream (2%) three times a day for 7 days
• paraffin ointment.
Betamethasone valerate (0.1%) is a potent (high strength) steroid.
The antibiotic mupirocin should be used on the infected area for a week. The most likely causative
bacterium is Staphylococcus aureus.
PART 1: ELVIS’S DERMATITIS AND ITS TREATMENT
1) What is dermatitis?
2) Explain the pathogenesis of dermatitis and what is happening to the areas of Elvis’s skin that are
affected.
3) Does inflammation cause dermatitis, or does dermatitis cause inflammation? Explain.
4) Which symptoms of dermatitis has Elvis experienced?
5) What are the main approaches in the treatment of dermatitis?
6) Which approach is used for Elvis? Is this the right approach?
7) Which class(es) of drugs are available to treat dermatitis?
Elvis was prescribed a stronger corticosteroid cream than the one he used previously.
8) What are the beneficial effects of corticosteroids in the treatment of dermatitis?
9) How are corticosteroids classified? (See Table 8.2)
Sunita takes the prescription to the pharmacy. The pharmacist confirms that Elvis has been
prescribed a stronger steroid—betamethasone valerate 0.1% in place of hydrocortisone 0.1%.
She advises Elvis to apply the steroid thinly, and not more often than prescribed, because, as a
potent steroid, it could cause side effects if absorbed. She also advises him not to use it on his
face.
10a) Why is it important to prescribe the lowest strength steroid that is effective?
10b) Why was Elvis advised not to apply the stronger steroid to his face?
10c) What are the side effects of topical steroids?
WORKBOOK 5 Dermatology: atopic dermatitis, acne, and psoriasis 207
The antibiotic and steroid cream help so much that Elvis decides he is cured and stops using
the emollients.
His dermatitis flares up 2 weeks later. The itching is very bad, and Sunita goes to the pharmacy
for something to ease it.
11) What is the role of emollients in the management of dermatitis?
12) Are emollients pharmacologically active? (See Box 8.2)
The pharmacist counsels Elvis to continue using his emollients even when he is without
symptoms.
Sunita tells her that he hates the greasiness of the ointment.
13a) Which form of emollient would be most suitable for Elvis to use on his face?
13b) When would be the best time for Elvis to use the ointment?
13c) Which is more effective, cream or ointment? Explain why.
Elvis asks the pharmacist what ‘vehicle’ means. He has seen the term on a website.
14) How might the pharmacist reply? Is the choice of vehicle important? Explain.
The dermatitis gets much worse over the next few months. Elvis is sent to see a consultant
dermatologist who tells him and Sunita about some more potent drugs used in dermatitis, but
says that they are reserved for use when all other treatments have failed.
15a) Give two examples of drugs that affect the immune system and are licensed to be prescribed by
specialists for dermatitis.
15b) Are these drugs used topically or systemically?
15c) When stronger steroids are given topically there is concern over their systemic effects. Should we
have the same concerns with topical use of a drug such as pimecrolimus? Explain your answer.
16) What is the mechanism of action of calcineurin inhibitors?
During the consultation, Elvis admits that he was not compliant with his previous treatment, and
is counselled by the dermatologist and specialist nurse on the importance of regular and
correct use of his medications. They decide that the best option would be to continue with the
same drug that was prescribed previously: betamethasone valerate 0.1% for 7 days.
After 1 week, Elvis should stop using the betamethasone valerate and continue using the
following emollients:
• lightliquidparafnbathadditive
208 Chapter 8 Inflammation and the skin: dermatitis, psoriasis, and acne
• emollientsoapsubstitute
• emollientcream
• parafnointmentatbedtime.
Sunita is dismayed at the lack of long-term progress with her son, despite the best efforts of the
medical profession.
17a) Can atopic dermatitis be cured?
17b) What do you think is the likely long-term prospect for Elvis and his skin condition?
One year later Elvis’ dermatitis is well controlled and he is happy that he does not have to use
the emollients quite as often.
PART 2
During a follow-up appointment, Elvis surprises his GP by asking the difference between
dermatitis and psoriasis. He says one of his teachers has psoriasis and a classmate has been
teasing him, saying that his dermatitis will turn to psoriasis in middle age. Elvis is worried that
this could happen.
18a) What is psoriasis?
18b) Describe the underlying pathology in psoriasis.
19) What are the characteristics of psoriatic skin?
The GP explains to Elvis that the two skin conditions are not related, and that dermatitis will not
lead to psoriasis. Some of the classes of drugs used in dermatitis are also used in psoriasis.
However, many treatment options for the two conditions are different.
20a) Consider the three treatment options for localized psoriasis listed below. Comment, in a single
sentence, on their usefulness.
Calcitriol
Acitretin
Dithranol
20b) Explain the role of emollients in the treatment of psoriasis.
21a) What are the effects of the vitamin D analogues used in psoriasis?
21b) Explain their mechanism of action.
WORKBOOK 5 Dermatology: atopic dermatitis, acne, and psoriasis 209
22a) What are therapeutic tars?
22b) List two characteristics of therapeutic tars that make them effective in psoriasis treatment.
22c) What are the disadvantages of tars?
23) Indicate some treatment options for patients with psoriasis that is unresponsive to the first-line
drugs. Suggest why they are not more commonly used.
Elvis is relieved. His dermatitis continues to improve steadily. He is extremely happy and
gratefulthathisskinisalmostcompletelynormal,whichiswhyhecanempathizewithhis
18-year-old cousin Eimear. She has severe acne affecting her face and back.
24) Describe the characteristics of acne.
25) How does acne arise?
Eimearhasbeenusinganover-the-counterbenzoylperoxide.Shedoesnotuseitregularly
because it dries out her skin. The acne seems to be getting worse. After she refuses on several
occasions to go out with friends because of the state of her skin, her mother Monique takes her
to see the GP. At the surgery the doctor examines her, and notes the types of lesions on her
face and back. They are blackheads with a few whiteheads; this is called comedonal acne.
AfterdiscussingherconditiontheGPrecommendsthatEimearregularlyusesbenzoyl
peroxide. Although she has used this already, she did so incorrectly. Because her acne is mild,
regular use of this drug should be sufficient. The doctor recommends a cream containing 2.5%
benzoylperoxide.Atthepharmacy,Eimeariscounselledonhowtousethecreamcorrectly.
She is told to apply it sparingly to the entire affected area, once a day at night-time for 2
months. Before she begins treatment Eimear should test her sensitivity by applying a small
amount behind her ear and looking for a reaction. The pharmacist also warns her that she will
probably experience irritation and dryness initially, but that with continued use these effects will
most likely disappear after a week or two.
26) How does benzoyl peroxide work to improve acne?
Over the next 2 months, Eimear’s acne gets progressively worse. Some spots are now pus-filled
and the redness and dryness are also disturbing her. Monique, who has been reading up on the
subject,askstheGPifhecouldprescribeazelaicacidinsteadofthebenzoylperoxide.TheGP
agrees,andprescribesazelaicacidwithanantibioticcream.HetellsEimearthatitoughttobe
less drying and cause less irritation, but asks her to return in one month if she sees no
improvement.
27) What are the effects and properties of azelaic acid that make it effective in acne?
Eimear returns to the GP after one month, as her condition is no better. The GP replaces the
azelaicacidwitharetinoidcreamtobeusedoncedaily.
210 Chapter 8 Inflammation and the skin: dermatitis, psoriasis, and acne
28) How do retinoids work to improve acne?
When she goes to collect the retinoid cream, the pharmacist advises Eimear to avoid exposure
to light, or at least to use a good broad-spectrum suntan lotion, while using the cream to reduce
the risk of skin irritation. She also advises that it should be used at bedtime.
Two weeks later Eimear forgets her medicine when she goes to visit her cousin Elvis for the
weekend. She asks a local pharmacist if she could borrow her cousin’s steroid cream and use it
short term to tide her over. One of her friends has told her that steroids will treat everything.
29a) Can steroids be used for acne?
29b) What advice do you think the local pharmacist should give Eimear?
The acne remains a problem. The doctor knows that combined hormonal contraceptives can
reduce acne in female patients. So when Eimear approaches him to discuss contraception, he
suggests co-cyprindiol, an oral contraceptive pill which should also improve her acne.
30) How does co-cyprindiol help in acne?
Eimear is happy! The hormone treatment is effective and her acne is largely resolved.
Chapter 9
Rheumatoid arthritis
Useful terms for this topic
Ankylosis: Loss of movement in a joint.
Cyclo-oxygenase: Key enzyme in the synthesis of
prostaglandins and thromboxane. Target for nonsteroidal anti-inammatory drugs (NSAIDs).
Chemokines: A subset of cytokines specically
involved in attracting immune cells during the
inammatory response.
Cytokines: Substances secreted by immune cells as
part of the inammatory response. They can affect the
function of the secreting cell itself, and/or other
immune cells in the vicinity.
Eicosanoids: Lipid mediators derived from the fatty
acid precursor arachidonic acid. The group
encompasses prostaglandins, thromboxane, and
leukotrienes.
Immunomodulatory drugs: Drugs that modulate a
specic aspect of the immune response.
Immunosuppressants: Drugs that dampen down the
overall immune response.
Interleukins: A subset of cytokines, which includes
tumour necrosis factors.
Pannus formation: Thickening and granulation of the
synovial tissue, which proliferates to ll the joint
space, causing destruction of the joint structure.
Synovial joint: A joint in which the opposing bones
are covered with a layer of hyaline/articular cartilage,
and which is enclosed in a capsule containing synovial
uid.
Imagine that your mum’s hands are so deformed that she
struggles to get her house key in the lock, and has had to
give up driving because she can no longer handle the gear
stick or the steering wheel. Although she takes regular
medication for her arthritis, she still suers from pain in
her joints and muscles, and to make things worse the
drugs cause nasty side eects, such as cataracts and
osteoporosis.
If this were the case, your mum would be among the 1% of
the population who suer from rheumatoid arthritis, one
of the commonest chronic inammatory conditions in
developed countries. Gwen and Pamela, whom we will
meet in Workbook 6, also suer from this condition,
which aects about 3% of men and 5% of women over the
age of 65.
Rheumatoid arthritis is a debilitating condition, with
one in three patients becoming seriously disabled.
It is characterized by intermittent worsening of
symptoms, or ‘ares’. Eective treatment usually
requires a multidisciplinary team of healthcare
professionals. It is crucial that each member of this
team has an understanding of the disease process and
treatment options, to ensure that the patient gets the
best possible care.
In this chapter we cover the pathogenesis of rheumatoid
arthritis, the cellular and molecular basis of action of the
commonly used drugs, and available strategies for
treatment. We also discuss the main adverse drug
reactions and contraindications, since these play a major
role in determining the choice of treatment. In Workbook
6 at the end of the chapter, the management of
rheumatoid arthritis is explored through our two ctional
patients, Gwen and Pamela.