Every time I sit down to write this report it seems there are new and more problems

that the primary care and the dermatology world in general have to face. It reminds

me of my borrowed phrase when moving into a large new medical centre 15 years

ago, when I warned my colleagues and staff that the only constant I could guarantee

was change!

If we listen to our current political masters we, as GPs, should be whooping with

pleasure at the power they are handing over to us, and the opportunity to configure

the future health service as we want. Notice the missing “National” since the

localising of commissioning is already and will, I believe, become ever more

post-coded. This means the blame will be passed onto our local heads and indeed for

some, the legal responsibility.

Where does this leave primary care dermatology or as I prefer to call it “care for

dermatology patients?” The Skin Care Campaign (SCC) is rightly concerned about

the future risk of high cost, rare and less glamorous diseases for which patients will

in future have to travel even longer distances for treatment, or not receive care at all.

In addition the lumping in of dermatitis as a minor ailment (at number two by

frequency of diagnosis to number one URTI) by the PAGB (Proprietary Association of

Great Britain) and supported by the great and the good in our RCGP. This makes us

very worried that patients with long term conditions such as atopic dermatitis will be

Primary Care Dermatology Society Spring 2011

Bulletinpcds.org.uk

Chairman’s Report

The PCDS Trustee Committee

Mr Peter Lapsley Dr Tom PoynerDr Stephen Hayes Dr Jane Rakowski Dr Julia Schofield

Epiduo Gel Abbreviated Prescribing InformationPresentation: 0.1% adapalene & 2.5% benzoyl peroxide Indications: Cutaneous treatment of acnevulgaris when comedones, papules and pustules are present. Dosage and Administration: A thin filmshould be applied to the entire acne affected areas once a day in the evening to clean & dry skin. If irritationoccurs, apply non-comedogenic moisturizers, use the medication less frequently, suspend use temporarily,or discontinue use altogether. Duration of treatment should be determined on the basis of clinical condition;early signs of improvement usually appear after 1 to 4 weeks. The safety and effectiveness of Epiduo havenot been studied in children below 12 years of age. Contraindications: Hypersensitivity to the activesubstances or to any of the excipients. Precautions and Warnings: Should not be applied to damaged,broken or eczematous skin, or come into contact with eyes, mouth, nostrils or mucous membranes (washimmediately with warm water if product enters eyes). Contains propylene glycol (E1520) which may causeskin irritation. Avoid excessive exposure to sunlight or UV light. Avoid contact with any coloured materialincluding hair and dyed fabrics as this may result in bleaching and discoloration. Epiduo should not be usedduring pregnancy. Interactions: No interaction studies have been conducted with Epiduo. There are noknown interactions with other medicinal products which might be used cutaneously and concurrently withEpiduo. However, other retinoids, benzoyl peroxide or drugs with a similar mode of action should not beused concurrently. Caution should be exercised if cosmetics with desquamative, irritant or drying effectsare used, as they may produce additive irritant effects with Epiduo. Absorption of adapalene & benzoylperoxide through human skin is low therefore interaction with systemic medicinal products is unlikely.

Undesirable Effects: Epiduo may cause the following localized adverse reactions: Common (≥ 1/100to <1/10): dry skin, irritative contact dermatitis, burning and skin irritation. Uncommon (≥ 1/1000 to≤1/100): pruritus and sunburn. Unknown (cannot be estimated from the available data): allergic contactdermatitis, swelling face. If skin irritation appears after application of Epiduo, the intensity is generallymild or moderate, with local tolerability signs and symptoms (erythema, dryness, scaling, burning andpain of skin (stinging pain)) peaking during the first week and then subsiding spontaneously. PackagingQuantities and Cost: 45g tube £17.91 (NHS) MA Number: PL 10590/0057 Legal Category: POM FullPrescribing Information is Available From: Galderma (UK) Limited, Meridien House, 69-71 ClarendonRoad, Watford, Herts, WD17 1DS. UK. Tel: +44 (0)1923 208950 Fax: +44 (0)1923 208998. Date ofRevision: November 2010.

Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.gov.uk.

Adverse events should also be reported to Galderma (UK) Ltd.

She wants fast results. You want long-term results.

NEWIntroducing an acne therapy that keeps

you both happy

This weekend This summer This time next year

Date of preparation: January 2011 EPI/508/0111Copyright © 2011 Galderma (UK) Ltd.

pushed into self diagnosis and purchasing treatments rather than being diagnosed by

a GP. Important and appropriate medication prescribed is currently free to children and

pensioners.

On both these counts we at the PCDS are working with many agencies (All Party

Parliamentary Group on Skin; Dermatology Council for England; BAD and the

Department of Health (DH)) to ensure that commissioners will be obliged to provide

full dermatology services in their area and not just the cheapest basic service,

whether that be by GPSIs or private providers. It is important not to neglect the

training and research provision that is so vital for the long term. That is not to say that

Intermediate care and training cannot be provided by GPSIs. Indeed the opposite is

true, however, a fully integrated service incorporating secondary and tertiary care is

essential and must also be protected. To this end there is a DH supported

multidisciplinary committee working at present to provide standards for

commissioners and previous work on accreditation requirements for GPSIs; which is

a little less proscriptive but similar to the 2007 regulations.

We must not let local commissioners think of dermatology as an easy target for cuts

when for years in many areas it has been woefully neglected and patients suffer as a

consequence. Recently in North London we heard of pharmacy advisors verbally

advising GPs not to prescribe any emollients (despite ever increasing evidence of

effectiveness) and to tell patients to buy them! Note, they did not dare to write it

down since I believe this is against the NHS act, which requires a doctor to prescribe,

needed medication. Please let us and everyone know of any such outrageous acts.

The SCC are particularly keen to be informed.

On a cheerful note the “Essential Dermatology” series of 10, repeated, one-day

courses for VTS registrars, specialist nurses and GPs whose dermatology knowledge

is less than comfortable starts in April. The venues are listed on the website and

advertised in Pulse. These are in addition to our usual high standard meetings and will

provide the essential knowledge for day-to-day care of the common dermatology

diseases. Please make these known to your registrars, VTS course organisers,

colleagues and commissioners/PCTs, whom we will be contacting but who may need

reminding. Partners may risk becoming deskilled if they are not at present by your

very presence as a skin authority in the practice!

Stephen Kownacki

Executive Chair

Editorial Spring 2011

I’m writing the Spring Editorial inspired by the fact

that our Christmas Camellia is finally flowering and

we also suddenly have a wonderful show of irises in

the garden. It seems like a long time since I planted

them. I’ve also managed to survive a family skiing

holiday without any injuries for which I am very

grateful.

It’s been a busy time for the committee recently.

We have been involved in writing the new GPSI

guidance which is currently at the Department of

Heath and will be released shortly. Stephen

Kownacki has already mentioned the Essential

Dermatology series that will be starting this April in

his report. We are also currently involved with other

Stakeholders in writing guidance on Dermatology

Standards that the new commissioners will be able

to use when PCTs disappear …

Jason Davies, a Histopathologist in North Devon

has kindly agreed to write a couple of articles on the

subject that we all struggle to get to grips with. The

first article, I’m sure you will agree, explains in

simple terms how histopathology can help in the

diagnosis of skin cancers. The next article will focus

on common inflammatory dermatoses.

I also have articles on top 10 fungal tips and

teledermatology in the pipeline, in addition to our

regular features. If anyone has any ideas on future

articles or recommendations of authors please can

you let me know.

I’m very grateful to Stephen Hayes, who recently

resigned from the committee, but continues to

work with us on a regular basis. The article that he

has written on exciting developments in treatments

of melanoma is well worth a read.

4

The vitamin D consensus statement is definitely

worth a mention for those who haven’t seen it. It

represents the unified views of the British

Association of Dermatologists, Cancer Research

UK, Diabetes UK, the Multiple Sclerosis Society, the

National Heart Forum, the National Osteoporosis

Society and the Primary Care Dermatology Society.

In summary it was agreed that Vitamin D is

essential for healthy bones and that the most

important source was from sunlight. It was thought

that the amount of time needed to make vitamin D

was dependant on physical, environmental and

personal factors. It was impossible to state an exact

time of exposure but was thought to be short and

less that the amount of time taken for the skin to

redden and burn. It was thought that a matter of

minutes in the middle of the day without sunscreen

should be sufficient and that people should become

familiar with their skin types and learn how long

they could be exposed before burning. Whether

vitamin D protects against chronic diseases such as

cancer, heart disease and diabetes, and the benefits

and risks of widespread supplementation needs

further research. Sounds like common sense to me.

Lastly the BBC news health reported that sap from

the common garden weed petty spurge appears to

treat non-melanoma skin cancers. This was from an

article published in the British Journal of

Dermatology. Results were promising, 41 out of 48

cancers had completely resolved after a month’s

treatment. More work is obviously needed as this

was a small study. Experts suggest not trying this

at home!

Helen Frow

5

Sewing with Christy

If you want to be an excellent Skin Surgeon, you need to

be good at every step of the procedure; from introducing

yourself and inspiring immediate confidence in your

patients, to explaining clearly why their surgery is

necessary, the risks and benefits of the procedure, and the

most likely outcome. The more you can put your patient at

ease, the more successful the operation will be. Once your

patient is relaxed and ready you should start by injecting your

local anaesthesia in the least painful way.

This short article will concentrate on why anaesthesia is painful,

the best agents to use, equipment to have available, plus a few

personal tips from me. I perform more than 2000 skin surgery

operations per year under local anaesthetic. The important point

to mention here is; the more operations you do the more you

will learn from your own experiences and that ultimately, you

will become a better Skin Surgeon.

The most commonly used agent in surface anaesthesia is

Lidocaine (Xylocaine is the trade name). It is safe because of its

rapid onset, low risk of producing allergic reactions and is

extensively used in general practice and plastic surgery. It is

almost entirely metabolised by the liver, and renal excretion is a

minor pathway in the elimination process, due to extensive

re-absorption (less than 10% of the administered dose is found

unchanged in the urine). Lidocaine along with other

anaesthetics should be used with caution in patients with

epilepsy, respiratory, renal, liver or cardiac impairment. The

maximum safe dose for healthy adults should not exceed

200mg in a single dose (ie 20 ml of the 1% Lidocaine). If close

to this amount of local anaesthetic is used during your surgical

procedure you really need to ask yourself if you should be doing

this in your clinic or should the patient be referred to hospital?

There are several reasons that local anaesthesia is painful. The

most obvious one is that the needle is sharp! Also, Lidocaine is

acidic (ph 4-5.) and the physical volume will push the dermal

stretch receptors to the painful limit. Cold anaesthetic, straight

from the fridge is more uncomfortable than injecting it at room

temperature.

The smaller the gauge of your needle, the less painful as it

reduces frictional pain when the needle pierces the skin. The

best needle to use is the 27 gauge (Green needle is 21, Blue is

23 and Orange is 25). A sterican ophthalmic needle is the same

length as the green needle, yet is more flexible and you will

use less local anaesthetic agent as you inject. The longer barrel

of the needle will cover a larger area with each entry, reducing

the number of times you need to enter the skin.

Here are a few personal tips to make the injection less painful.

Relax and prepare the patient. A friendly, chatty assistant, who

distracts the patient and holds their nervously, shaking hands is

so important to reassure the patient and make them feel at

ease. Always use local at room temperature, massage and

manipulate the skin next to the injection site and inject slowly.

6

Plain local is less painful than those with added

Adrenaline. Always try to inject into the

subcutaneous tissue – although it will take longer

for the local to take effect ... be patient Doctor, it is

worth it in the end! Ask the patient to concentrate

on deep breathing and count in their head slowly to

a hundred – all steps to distract the patient. If Emla

cream (a combination of Lidocaine and Prilocaine) is

used, it must be applied to the site at least 90 mins

before the procedure. Preferably cover the Emla

with a film dressing such as Tegaderm or Opsite to

retain a thick application of the cream at the

injection site for the full 90 minutes.

After administering the anaesthetic always check

the patient is pain free before you start your

procedure. If you have to interrupt the operation half

way because the patient is experiencing pain, you

will have to remove your sterile gloves, draw up

extra local, re-inject then scrub up again. You will

disturb your surgical train of thought, increase the

risk of infection and above all it is very annoying. A

frustrated Surgeon tends to make more mistakes!

To test that the local anaesthesia is working

properly before you start your procedure, gently

press your needle tip to the injected area which

should appear white from infiltration by the local. Do

not simply ask whether they can feel the needle,

because they will be able to sense pressure due to

the stretch receptors in the skin, which have a

thicker myelin sheath and are less sensitive to the

actions of local anaesthetic. In other words the

patient will still feel pressure and touch sensations.

If local anaesthetic is injected close to a muscle it is

important to explain to your patient that there may

be temporary muscle weakness. Patients won’t

panic if they know what to expect.

One of the problems of plain Lidocaine is that it is

relatively short acting and does not allow you to

perform longer procedures. To get around this

problem the addition of Adrenaline to the Lidocaine

causes vasoconstriction, which prolongs the action

of the anaesthetic. This has the added benefit of

producing less blood in the operating site making it

easier for the Surgeon to see the tissue definition.

The combination of Lidocaine and Adrenaline also

reduces the amount of local anaesthesia used

making it much safer for the patient.

When using Lidocaine with Adrenaline in areas

supplied by end arteries such as the fingers, toes

and penis, there is a theoretical risk of tissue

necrosis, so, it is safer to use plain Lidocaine. It is

however safe to use this combination on the tip of

the nose as it is extremely vascular on the face.

Lidocaine with Adrenaline is routinely used in

plastic surgery on the nose without causing any

problems. But, if in doubt or, in cases where

patients have severe peripheral vascular disease or

uncontrolled diabetes then a low concentration of

Adrenaline 1 in 200,000 in 20ml should be used or

avoid Adrenaline all together.

Side effects from local anaesthetic are rare when

used within the safety dose. However, toxic

reactions are likely to occur when used in high

volumes or if accidental intravascular injection

occurs. Toxicity often presents as a sensation of

numbness or tingling. Other adverse reactions

include visual disturbance, anxiety, dizziness and

altered sensation around the lips and mouth. As

the toxic level increases patients may experience

slurring of speech, muscle twitching and seizures.

To minimise the risk of intravascular injection it is

recommended to aspirate prior to injection. If you

are using a small gauge needle, which will not

aspirate blood, insert the needle to the furthest

point, then inject while withdrawing the needle

towards you. Keep moving the needle while slowly

injecting small amounts.

In the next bulletin, I will describe the different

methods of administering local anaesthetic such

as field and nerve block. In the meantime practice

safely and enjoy cutting and stitching.

Christy Chou

I N T E L L I G E N T LY R E S T O R E D R Y S K I N

Name of the Class I Medical Device: Balneum Cream.Ingredients: Urea 5 %, Ceramide 3, Aqua, Glycine Soya Oil,Propylene Glycol, Cetearyl Alcohol, Liquid Paraffin, Isohexadecane,Sodium Lactate, Lactic Acid, PEG-20 Stearate, Polysorbate 60,Squalane, Stearic Acid, Disodium EDTA, Lecithin, Tocopherol,Ascorbyl Palmitate, Hydrogenated Palm Glycerides Citrate.Balneum Cream is free of fragrances, colourants and preservatives.Pharmaceutical form: Cream. White cream. Indications: For thesymptomatic relief of dry and very dry skin conditions. Dry and verydry skin is often associated with eczema, psoriasis and otherdermatological conditions in which the skin has low levels ofsubstances such as urea, ceramides and lipids. Balneum Creamcontains clinically proven ingredients such as urea, ceramide 3 and

lipids. It is formulated to protect the skin, to maintain skinmoisturisation and to restore the impaired skin barrier in conditionsgiving rise to dry skin. Method of administration: Using cleanhands, apply the cream to the skin twice daily. Contraindications:Patients with known hypersensitivity to any of the ingredients.Warnings and precautions: For external use only. Do not use onbroken or inflamed skin. Caution should be exercised withconcomitant use of some medicated topicals. If the conditionworsens on usage or if patients experience side effects, discontinueuse and consult a Health Care Professional. Undesirable effects:Very few side effects have been reported; typically local skinreactions. Special precautions for storage: Do not store above25°C. Use within 6 months of first opening. Pack sizes: Available

in 50g (£2.80) and 500g (£9.80) pump dispensers. CE markingheld by: Almirall Hermal GmbH, Scholtzstraße 3, 21465 Reinbek,Germany. Distributed in the UK by: Almirall Ltd, 4 The Square,Stockley Park East, Uxbridge, UB11 1ET.

References: 1. Balneum Cream label. 2. Puschmann M et al.Clinical Experimental Evaluation of the Effectiveness and Tolerationof a Urea-Ceramide Combination in Dry Skin. Akt Dermatol 2000;26: 70-75. 3. Cork M, Danby S. Skin Barrier Breakdown: ARenaissance in Emollient Therapy. British Journal of Nursing 2009;18(14): 872-877.

Date of preparation:January 2011. UKSOY0638.

Don't just rehydrate, help to restore the skin's natural barrier.1,2,3

A D VA N C I N G E M O L L I E N T T H E R A P Y

Urea 5% and ceramide 3

ANADVANCE

IN DRY SKINTREATMENT

8

Paediatric Vulval Problems

Introduction

Paediatric genital problems in childhood are less

common than in adults and occur more frequently

in females than males. I am unable to cover all

possible diagnoses in the next few paragraphs and

will instead focus on the most common problems

and their treatment.

The physiological differences between the vulva

due to the lack of oestrogen before puberty

explains many of the symptoms observed. It is also

important to appreciate that children may not have

the vocabulary to explain irritation and discomfort

in the anogenital region and this can sometimes

lead to behavioural problems and night terrors.

Vulvitis

In children the vulva is thin, easily damaged

epithelium with an absence of the lactobacilli

which are found post menarche. This makes

irritation from soaps and bubble baths more likely

with the possibility of secondary infection with

common skin infections rather than Candida

albicans. Inflammation in the vulval area is called

vulvitis.

The commonest causes of vulvitis (Fig 1) are;

• Atopic vulvitis

• Irritant Vulvitis

A history of eczema will increase the risk of vulvitis.

The disorder is easily managed by the following:

• Avoidance of soaps or bubble baths

• Wash with an emollient as a soap substitute

• Use an emollient each night on the genital region

before bed-time

• Treatment with mostly mildly potent topical

steroids without antifungal preparation for up to

6 days per month if needed

• Consider taking bacterial swabs of the area since

pain and discharge may be associated with a

staphylococcal or streptococcal infection

PsoriasisThis will often occur in the anogenital region in

children. It will often look worse than it feels

presenting as erythematous well demarcated vulval

skin lesions (Fig 2) which cause alarm to parents.

Dr Ruth Murphy PhD FRCP

Consultant Dermatologist, Queens Medical Centre, Nottingham

9

Whilst it is possible to completely control and

eradicate atopic vulvitis it is almost impossible to

completely clear genital psoriasis although it can be

managed so that symptoms are well controlled.

Treatment is similar for atopic vulvitis:

• Avoid irritants such as soap

• Use emollients to wash with

• Apply emollient each night before bed

• Consider secondary staphylococcal or

streptococcal infection

• Treat the inflammation with Trimovate ointment™

for up to 6 days per month

Lichen SclerosusThis is an autoimmune condition which causes

inflammation and thinning of vulval skin. It is often

itchy and on examination appears as white areas in

a figure of eight around the clitoral hood and

extending to the anus. The thinned skin is prone to

haemorrhage and tears easily (Fig 3). Patients may

present with constipation and issues around toilet

training. It is worth examining the skin elsewhere

for cutaneous patches. This condition is life long

and requires appropriate management to avoid

scarring. It is most often treated as thrush which I

have already explained in a pre-pubertal age group is

a very unlikely diagnosis. Suspected cases need

referral to secondary care.

Treatment of Lichen sclerosus is as follows:

• Avoid irritants and soaps

• Use emollients to wash with

• Switch off the inflammation with a decreasing

course of potent topical steroids with Clobetasol

Propionate ointment with the appropriate

specialist guidance.

ConclusionIn general it is possible to treat many vulval problems

in children with simple measures such as

discontinuation of soaps and bubble baths and use of

emollients. Most cases of vulvitis will easily be

managed in primary care. Other conditions such as

lichen sclerosus, vitiligo, aphthous ulceration etc may

need specialist input. It is important to remember that

vulval irritation in children is not likely to be thrush.

10

Understanding the Histology Report: Part One – Skin Cancer

Introduction

In this short article I will try to cover some of the main

problems and causes of confusion in histology reports. It is not

intended to be comprehensive but I hope that I can provide

some useful learning points.

Histology is useful for primary diagnosis and checking

diagnostic-accuracy, for providing prognostic information and

for medicolegal purposes. Always submit removed specimens

for histology. I have encountered several cases of recurrent or

metastatic melanoma where the previous “seborrheic wart”

had been thrown away.

Help the histopathologist by providing good clinical information,

including full patient demographics (usually computerised

anyway) and the lesion’s site and duration. The lesion’s

behaviour, appearance and stage of evolution are helpful.

Remember, formalin significantly changes a specimen’s

appearance and knowledge of the original colour may be useful

(e.g. Spitz naevi may be pink).

The histology report should be concise with clear diagnostic

and prognostic information, adhering to Royal College of

Pathologists (RCPath) minimum datasets (MDS). The RCPath

produces MDS for various tumour sites including skin1. This

document covers the common skin tumours. It is a concise,

useful reference and is available for download2.

The report should have sensible clinico-pathological correlation

and, if necessary, provide some advice on unusual diagnoses.

If the diagnosis is unexpected and not compatible with the

clinical picture then ask for a review, preferably at the local

multidisciplinary team meeting (MDT).

The excisional biopsy is most useful in the treatment and

investigation of skin tumours, and is the preferred method when

excision margins need to be assessed. Smaller biopsies produce

an increased risk of sampling error. Multiple rather than single

punch biopsies may help reduce this.

If removing facial lesions, where resection margins are more

critical, you might consider orientating the specimen. Use a

simple and consistent method, preferably with just one suture,

with or without diagrams for yourself and the pathologist. Use an

open loop so that the knot does not impinge on the skin, else the

specimen might be damaged during suture removal.

Resection margins are examined histologically using India ink

and other dyes, and carefully measured. Accuracy of

measurement can be agreed locally (e.g. “>1 mm” rather than a

specific measurement like “1.85 mm”). Recurrence is possible

even when margins are reported as “clear” for various reasons.

For example, tumours often appear as multiple separate nodules

with normal tissue between, rather than a single solid sheet –

though 3-dimensionally, these nodules may well link up. One of

these apparent nodules might “skip” onto the other side of the

resection margin. Fixation can shrink the specimen (and

therefore the size of the histological margin) by up to one third.

The wax tissue blocks produced from the specimen are up to

3 mm thick, but, after trimming, the material on a histology slide

Dr Jason Davies

Consultant Histopathologist, North Devon District Hospital, Barnstaple

11

is only around 1/1000th of that (3 microns). So only a tiny

fraction of the specimen is actually viewed microscopically.

“Deepers”, “levels” and “serial sections” are all terms for

laboratory methods that involve cutting deeper into the wax

tissue block, to examine other areas (Fig 1). They all help reduce

the chance of sampling error.

Immunohistochemistry

Immunohistochemistry has largely displaced the use of special

stains in cancer diagnosis. It provides a method of

demonstrating specific antigens on a tumour cell and can help in

the differential diagnosis of morphologically similar tumours, in

separating benign from malignant lesions, in searching for early

invasion and in confirming provisional histological diagnoses.

Table 1 shows some of the commonly used antibodies that you

might see in histology reports.

Usually, a panel of several different antibodies is applied. As a

simple example, there are a variety of malignant spindle cell

tumours of the skin that look similar. A basic panel might show

no staining for S100 and MelanA (both melanoma markers) nor

for desmin (a muscle marker) but have positive staining for the

epithelial marker AE1/3, by which we could deduce the tumour

to be a spindle cell carcinoma.

Basal Cell Carcinoma (BCC)

The MDS groups BCCs into a low risk “nodular” group, and a

high risk group composed of the superficial, infiltrative/

morpheic and micronodular types (Fig 2). These are high risk

because all have either an increased chance of local recurrence,

of incomplete excision, of aggressive local behaviour or a

combination of these problems.

Very early BCCs and squamous cell carcinomas (SCC) can look

histologically similar, and BCCs can keratinise and look like SCC.

Immunohistochemistry, using a panel of just two antibodies,

can help their separation; BCC is BerEP4 positive, and EMA

negative, whilst SCC is the opposite (i.e. BerEP4 negative, EMA

Fig 1: Initial levels on the left slide showed normalskin. Levelling further through the block eventuallyrevealed BCC in arrowed section

Fig 2: A tongue of micronodular BCC has arisen inan overlying nodular BCC, and extended down tothe deep resection margin (arrow)

Fig 3: Positive staining (brown colour) for theantibody BerEP4 in a BCC

12

positive) (Fig 3). Most so-called basisquamous tumours stain

similarly to basal cell carcinomas, suggesting they are related

to the latter.

Squamous Cell Carcinoma

SCCs can arise in both actinic keratoses and Bowen’s disease,

both in-situ lesions with epidermal atypia/dysplasia (i.e.

abnormal cells). It can be very difficult to assess the very early

stages of invasion, which is usually seen as small tongues of

atypical squamous epithelium extending into the dermis.

However, several processes can closely mimic early invasion.

For example, the atypical epidermis can extend down eccrine

ducts and look invasive, as can crosscutting of the in-situ

component in a poorly orientated specimen (especially

fragments from curettage). These all might lead to uncertainty

in the histology report.

SCCs are graded as well, moderate, poorly or undifferentiated

tumours, which correspond with the alternative Broder’s

system of 1 (low grade) to 4 (high grade). Pathologists often

disagree about grading, in all tumour types, not just those in

the skin: a tumour that is called well differentiated by one

might be moderate to another.

Pathologists will measure the thickness of an SCC, as it is

required for staging, and will also provide a Clark’s level of

invasion, which you might be more used to seeing in reports of

malignant melanoma (Table 2).

Keratoacanthoma (KA)

Pathologists differ in their willingness to diagnose KA as a

separate entity; some believe they are simply variants of

well-differentiated squamous cell carcinoma. Even if KA is

diagnosed, many will add a sentence to say that SCC cannot be

excluded. Whilst some experts might accept biopsies, most will

want to see an excision biopsy, as the architecture can be the

key to diagnosis. If the pathologist is thinking about KA, you are

likely to see phrases such as “cup-shaped” or “crateriform” and

“ground-glass squamous epithelium”

Melanocytic Lesions

Dysplastic naevus can be difficult to diagnose histologically and

the threshold for diagnosis varies between pathologists. At one

end of the spectrum, there may be defensive over-diagnosis of

benign naevi as dysplastic, and in this circumstance you may

see a phrase such as “a naevus with some dysplastic features”.

Table 1: Some Common Immunohistochemical Antibodies

Tissue Type Antibody Comments

Melanocytic S100MelanA, HMB45

– sensitive but less specific (also stains neural tissue, etc)– more specific, less sensitive

Epithelial AE1/3Cam5.2CK 7, 20EMABerEP4

Smooth Muscle Smooth Muscle Actin (SMA)Desmin

Vascular CD 31, 34Factor 8 antigen

Lymphoid LCACD20CD 3, 4, 5, 8CD68

– Most Lymphocytes– B Cells– T Cells– Histiocytes

13

At the other end of the spectrum, their appearance merges with

in-situ malignant melanoma (MM), and these are sometimes

termed severely dysplastic.

Our practice is for MDT review of all possible dysplastic naevi.

We aim for complete excision in confirmed cases, and consider

wider excision for those described as severely dysplastic.

Some other terms that you might encounter in reports include

“Pagetoid” (after Paget’s disease of the nipple which it

resembles) which is a “buckshot”-like spread of melanocytic

cells into upper layers of epidermis (Fig 4). It is usually a feature

of superficial spreading MM. Lentiginous spread means single

melanocytes along the basal epidermis (e.g. in lentigo maligna).

Malignant Melanoma

The diagnosis of malignant melanoma can be difficult, and

research has shown that even expert pathologists can fail to

agree on the seemingly straightforward separation of benign

from malignant lesions3.

Melanoma can be an in-situ lesion (confined to the epidermis) or

invasive (infiltrating dermis). Melanomas are also separated into

2 different biological growth phases, which help predict their

behaviour, and these can cause some confusion.

The radial growth phase (RGP) includes both the in-situ lesions

and those showing the very earliest stage of invasion by a few

cells (so called micro-invasion). Theoretically, these have no risk

of metastasis.

However, in vertical growth phase (VGP), a more advanced

stage with a greater volume of invasive tumour, the melanoma

has metastatic potential.

The best prognostic indicator in melanoma is the lesion’s

thickness (the “Breslow depth” – measured from the granular

cell layer at the top of the epidermis to the deepest point of

tumour in the dermis), whilst the second most important

variable is the presence of ulceration, particularly greater than

3 mm. Both these indices have fairly good agreement between

pathologists and are used in the staging of melanomas.

Remember, if the melanoma is in-situ it will not have a depth.

References1. Minimum dataset for the histopathological reporting of common skin cancers –February 2002. Royal College of Pathologists

2. http://www.rcpath.org\resources\pdf\skincancers2802.pdf

3. Discordance among expert pathologists in diagnosis of melanocytic neoplasms.A. Ackerman. Human Pathology, Volume 27, Issue 11, Pages 1115-1116.

Table 2: Clark’s Levels for Malignant Melanoma and SCC

I Confined to epidermis (ie. in-situ, non-invasive)

II Invasion of papillary dermis

III Fills papillary dermis

IV Invasion of reticular dermis

V Invasion of subcutaneous fat

Fig 4: Pagetoid spread of melanoma cells labelled red with the antibody MelanA

14

Melanoma Sudy Group

The winter meeting of the Melanoma Study group was

held at the Royal Marsden Hospital in London on Friday

28th January, with 90 attending. The first presentation

discussed ultrasound with guided needle biopsy as a less

invasive potential alternative to sentinel lymph node biopsy

(SLNB) for staging melanoma. The speaker, Meiron Thomas,

felt SLNB was overrated. Interesting case reports were cited,

for example a surgeon, returning from an international

conference with a renewed interest in SLNB, did it on patients

who had been apparently disease free for 4 years since their

original surgery, finding occult micro metastases in some,

which had presumably sat there indolently for years.

Evidence was shown of melanoma being transferred via a

transplanted kidney, where the donor had been clinically

disease free for years. This was put down to occult dormant

micro metastases taking off in a new immune suppressed

host. Since we cannot detect micro metastases in vivo, this

raises all sorts of unanswered questions.

There was lively debate and no conclusion was reached. SLNB

is an invasive staging procedure which has not been

conclusively shown to improve survival. One issue around

lymph node biopsy that was raised, was that the benefits of

staging melanoma were questionable as we had no effective

therapy for metastatic disease. This, however, might change

soon, as we would hear from later speakers.

Better results from more radical node clearance?

Plastic surgeon Andrew Hayes advocated a more aggressive

surgical approach to ilio inguinal lymph gland dissection for

lower limb melanoma patients with inguinal spread. He

reminded us that the anatomical sub divisions we apply to the

various lymph gland basins were arbitrary: the lymphatic system

is a unitary whole. If groin glands were palpable, then iliac

glands would likely be involved. Also, our staging techniques

aren’t as good as we’d like, with many cancerous glands

undetected by PET scans, especially deep pelvic (obturator)

glands. He said many surgeons missed involved obturator

glands as it was so challenging to operate behind the iliac vein.

He said he ‘believed but couldn’t prove’ that patients with

biologically less invasive melanomas often experienced long

term survival or cure after radical removal of the deep pelvic

glands.

Another plastic surgeon explained how a new understanding of

cutaneous vascular anatomy was allowing better flap survival.

He also showed us a tour de force of heroic excisions and

reconstruction of catastrophically neglected scalp cancers. I

don’t think even the most experienced GPSIs should remove

the top of the skull, replace it with a titanium moulding and

swing a hand sized rotation flap over to cover the robo-cranium

and split skin graft the defect. I think we’ll leave that to the

glory boys.

15

BRAF and other melanoma mutations

If astounding advances are being made in plastic surgery, these

are arguably eclipsed by the new knowledge of the nature of

the genetic mutations which drive melanoma and the tools this

knowledge is giving oncologists. 50% of melanoma mutations

are BRAF, 25% NRAS and there are a few others. The

excitement has spilled over into the national press due to the

Plexxicon (TM) drug PLX4032 which targets BRAF mutations.

Some before and after PET scans showed liver and bone

secondaries shrink dramatically in 15 days. There are several

marvellous new drugs in trials, hoped to be marketed within 18

months.

Major side effects to wonder drugs

We heard that side effects had been somewhat played down.

Nearly all patients suffer skin problems including toxic

erythema, photosensitivity rashes and erythema nodosum. Of

more concern, a third of patients get squamous cell cancers

within months of starting therapy. These SCCs are apparently

sitting there sub clinically until the anti-BRAF drug releases

them (biology too complicated for me). Thankfully these

tumours are on the milder ‘keratoacanthoma like’ end of the

SCC spectrum and easily treated, but details are still scanty.

Polyarthralgia is also a problem with PLX4032, and price may be

as well.

Oncolytic viruses

The last excitement of the day concerned oncolytic viruses

which are once again being trialled. Several wild and

genetically modified viruses are being used, either

intravenously or directly injected into metastatic tumours.

Again, no trials but some impressive case studies. A

secondary deposit by the shoulder shrunk visibly after intra

lesional virus injection. CT scans showed distant metastases

shrinking also despite no other injections being made. A

biomed company which owns one of these GM viruses has

just changed hands for £400 million, prompting speculation

that someone might know something big!

Membership of the Melanoma Study Group is open to any

doctor or nurse involved in melanoma research or care.

Please see the web site for further details. The above is an

edited highlights of the day as seen by the only GP on the

Group. Much of it was above my head as this is mainly a

group for top specialists and researchers. Clearly these are

exciting times as far as the management of advanced

disease is concerned.

Stephen Hayes

December 2010 – January 2011

In a recent moment of clarity, it struck

us here at PCDS Towers that, by the

time we have written these articles,

they have been collated, edited,

processed, type set, printed and sent

out to you, our topical and timely

salutations bear little resemblance to

the real world. I would consequently

like to be the first to wish you a Happy

Christmas and hope that you enjoy the

coming Olympic Games, in Rio.

I start, this bulletin, with a trio of papers

from across the globe1,2,3. Apart from the

ongoing debate as to whether it should

be ‘dermatoscopy’ or ‘dermoscopy’,

these papers illustrate an exciting part of

our working lives. When any new

technique is developed, one of the first

things that needs to be decided upon is

its vocabulary. Then comes the most

useful applications, then the esoteric. We

are at the point where the dermoscopy of

the common lesions is fairly well

understood but we have yet to head

down in to the backwaters of the truly

bizarre. In these papers we have an

attempt to differentiate between

pigmented actinic keratoses and lentigo

maligna (you can’t), to try to create a

diagnostic algorithm for pyogenic

granulomas (you can’t) and to try to

determine characteristic features of

nonpigmented eccrine poromas (structures reminiscent of frog spawn, seeing as

you ask). We often look at dermoscopy as the next big thing, but we must

recognise and understand its limitations. Timely advice.

Another pair of papers. Firstly, from Northern Ireland4 is a population study looking

at attitudes towards sun bed use, suncare and sunburn in a region where there

has been two decades of sun-related health care campaigns. Sun care knowledge

was shown to be good, but there were major barriers to continuing improvement.

Men, in particular, appear resistant to sun care advice. Women have entrenched

attitudes towards the ‘attractiveness’ of a suntan and there is a common lack of

knowledge between both sexes of what an individual’s skin type is. More

encouraging is that sunbed use, as a result of recent campaigns, is falling. This,

however, is tempered by a companion paper from CED5. Here, the investigators

used a modified CAGE questionnaire to look at tanning behaviour in frequent

users of sunbeds. They showed the behaviour in a significant proportion of these

users to be representative of addiction. 41% showed ‘tanning addictive disorder’,

a further 33% showed ‘problem tanning behaviour’. This was particularly linked to

female gender and an early age of first tanning ‘fix’. I find this fascinating and

disturbing in turns.

A question I find myself pondering, in quiet moments, is whether Queen Elizabeth

I suffered from frontal fibrosing alopecia (FFA)? Her portraits may suggest this, but

we may never know for sure. What we do now know , as a consequence of work

from California and London6, is that FFA is accompanied by combinations of

hairline recession, scalp pruritus, perifollicular erythema and loss of the eyebrows

at presentation. As a rare disease, treatment strategies are poorly determined, but

here it is shown that hydroxychloroquine, used early, can give significant benefit –

at least for the first six months of use anyway.

We shall return to the scalp in a moment, pausing briefly to consider the

association of isotretinoin and depressive symptoms. This has long been a source

of contention – indeed, part of the consent process revolves around the reporting

of mood changes and depressive symptoms in individuals who take isotretinoin. A

nicely written paper from Bath7 goes a long way towards putting this particular

JournalWatch

16

shibboleth to bed. Basically, isotretinoin improves the quality of life indices of

those who take it for severe acne – particularly in those who were depressed at

the outset of treatment. I italicise this for emphasis – we sometimes forget that

acne itself is a condition that leads to depression and even suicide. This study

suggests an improvement, not a deterioration in mood in isotretinoin takers.

Powerful stuff indeed.

Hair is one of those human Goldilocks features – everyone seems to have either

too much or too little, rarely just the right amount. Androgenetic alopecia (AGA)

can affect both men and women, and even occasionally, adolescents. Amazingly,

there are little or no evidence based guidelines on the diagnosis and management

of this common and often distressing condition. This paper8 is the first step in that

process, giving definitions of AGA and presenting a consensus statement for sex

dependent stages in diagnosis. The definition is particularly interesting – ‘a

progressive non-scarring miniaturisation of the hair follicle with a characteristic

pattern in genetically predisposed men and women’. The hairs are often still there,

just too small, fine or fragile to see. Investigation is also interesting – the

suggestion is that it is not necessary to investigate men, but women should have

thyroid function, ferritin levels and free androgen index measured. I presume a

similar paper will be forthcoming on the treatment of this disorder, sadly I expect it

may be very short.

I make no apologies for including this next paper9. I must admit I had never heard

of mal de Meleda, nor am I ever likely to encounter a case but I think it joyous to

discover that there is a gene called SLURP1. For the record, it encodes a

lymphocyte antigen activator related protein. I think it sounds fab!

The regular reader of this column will have seen several papers showing that

psoriasis should really be considered to be a multi-system disease that just

happens to have a cutaneous manifestation. The increased incidence of ischaemic

heart disease is well documented, but the atherosclerosis that accompanies this

can also be a factor in the development of erectile dysfunction10. In psoriasis, this

appears to be almost 50% more common than in a matched control group –

although, in mitigation, psoriasis is probably not an independent risk factor. In an

increasingly holistic speciality, should assessment of sexual function become

routine for attendees at dermatology departments?

Now a first. I don’t think the humble tomato has been mentioned in these pages

before. Tomatoes, as I’m sure you know, are rich in lycopene – an increasingly

interesting antioxidant compound. It has been shown to be protective against

ultraviolet induced Erythema. Taking this one step further, this study11 takes a

group of women and feeds them either 55g of tomato paste rich in lycopene in

olive oil, or just the olive oil alone...for 12 weeks. This dose was shown to be

photoprotective as the experimental subjects had sequential skin biopsies taken

from both UV exposed and non-exposed sites. A remarkable study – not the least

because 55g of tomato paste is quite a quantity and to eat this every day for 12

weeks must demonstrate a degree of dedication on the part of the subject.

Contentious subject, number 873 – Vitamin D and UV radiation. Sometimes

research is needed to create an evidence base, even where the outcome seems

to be plain common sense. As here12. Serum Vitamin D increases with increasing

exposure to the sun. This increase is dependent upon the dose of UVB received.

However, if these doses of UVB are less, then the area of body exposed must be

greater to achieve the same levels of

serum vitamin. No wonder the Finns are

fond of naked bathing.

We near the end – for this bulletin. I reckon

one of the most frustrating dermatological

conditions to treat must be hidradenitis

supprativa – one can only imagine what it

must be like to have to suffer it. At least,

after this useful paper from The

Netherlands13, there is at least some

evidence to base treatment, or referral,

decisions upon. Although a small study

(only 12 subjects), acitretin was used as

monotherapy to treat cases that were

refractory to other treatment modalities.

The results were very encouraging with all

subjects achieving remission – this

remission was relatively long lived, in one

case the subject remained disease free

after 4 years. Hope, perchance?

Finally, a disease about which we have

only really scratched the surface –

delusional infestation (sorry!). It is a

disease that is considered rare, but

incidence data only really exists for

Germany. This paper14 attempts to look at

prevalence, treatment strategies and

assesses the feasibility of a randomised,

controlled trial. Although still rare, it would

appear that it is more common than

previously thought with a three year

prevalence around 5 cases per million

population. This would mean that most

dermatology departments will see it on a

regular basis. Treatment seems to still

revolve around the use of antipsychotic

medications, but the numbers appear too

small to make a true trial of treatments

feasible.

So there you go. Only 2 months of

journals, but a lot to digest. I’m off for a lie

down in a darkened room!

Julian Peace

References1. Akay et al – Dermatoscopy of flat pigmented faciallesions: diagnostic challenge between pigmentedactinic keratosis and lentigo maligna.BJD2010;163:1212-1217

17

18

Still snow on the ground this morning and I spend my driving time

avoiding potholes. Some are so big I’ve seen Chilean miners climb

out of them! At Christmas I bought my wife a torch – it was nice to

see her face light up!

Spring is around the corner and as the buds begin to appear the

kernels of the Scottish programme also rears its head above the

ground. Last year’s delegates were balloted on choosing between

two venues. Westerwood won by a convincing majority to have the honour of hosting

us on 12th -13th November, so pencil it in. It is good news for you golfers out there

with a Seve Ballesteros designed course attached to it. I’ll have to start thinking of

more golf jokes – oh here is one! A “James Joyce” a putt that is impossible to read.

Other educational meetings in Scotland include the PCDS Essential Dermatology day

on May 26th which will be well attended with the added bonus of an excellent

delegate pack with learning notes and a data stick. It would be ideal to send your GP

registrars along to as well.

The NW Glasgow CHP GP forum is to hold educational slots in their forum evenings

looking at patient pathways in dermatology and orthopaedics. If you are in this area

keep your eye out for them.

The Skin Care Campaign Scotland held a MSP briefing meeting at Holyrood on 9th

February presenting the SIGN guidelines on psoriasis and psoriatic arthritis plus

presentations on acne, eczema, leg ulcers and vitiligo. Work commitments prevented

me going but it was well received. One point they did make was that dermatology has

dropped out of the NES curriculum for GP registrar training and less than 200 of the

4960 Scottish GPs have been trained to diploma level in dermatology.

There are plans for a conference for GPSIs, clinical assistants & hospital practitioners

on Friday night and Saturday morning of 6th-7th May. The proposed venue is Crieff

Hydro. Further details are obtainable from your local Leo rep. I think our friend Ivan

Bristow, podiatrist from Southampton has been invited to speak. His jokes are usually

worse than mine but he is an excellent speaker.

The Dermatology Council for Scotland meets on 3rd March and will have the same

agenda as the cancelled meeting in December. This includes education and training,

service and Scottish Health Department issues. If anyone has anything they wish to

bring up let me know and I shall report it to them.

We are awaiting the SMC decision on Epiduo for acne and I will let you know the

result at the next bulletin.

That’s all for now as it has been a quiet period but things will warm up.

One final golf term – an “Arthur Scargill” – great strike but poor result.

Iain Henderson

News From North ofthe Border

2. Zaballos et al - Dermoscopy of pyogenicgranuloma: a morphological study.BJD2010;163:1229-1237

3. Minagawa et al – Dermoscopic features ofnonpigmented eccrine poromas in associationwith their morphological features.BJD2010;163:1264-1268

4. Boyle et al – Trends in reported sunbed use,sunburn, and sun care knowledge andattitudes in a UK region: results of a study ofthe Northern Ireland population.BJD2010;163:1269-1275

5. Harrington et al – Addictive like behavioursto ultraviolet light among frequent indoortanners.CED2010;36:33-38

6. Samaro et al - Frontal fibrosing alopecia: aclinical review of 36 patients.BJD2010;163:1296-1300

7. McGrath et al – A prospective trial of theeffects of isotretinoin on quality of life anddepressive symptoms.BJD2010;163:1323-1329

8. Blume-Peytavi et al - S1 guideline fordiagnostic evaluation in androgenetic alopeciain men, women and adolescents.BJD2011;164:5-15

9. Tjiu et al – SLURP1 mutation-impaired T-cellactivation in a family with mal de Meleda.BJD2011;164:47-53

10. Goulding et al – Erectile dysfunction inpatients with psoriasis: increased prevalence,an unmet need, and a chance to intervene.BJD2011;164:103-109

11. Rizwan et al – Tomato paste rich inlycopene protects against cutaneousphotodamage in humans in vivo: a randomisedcontrolled trial.BJD2011;164:154-162

12. Bogh et al - Interdependence betweenbody surface area and ultraviolet B dose invitamin D production: a randomised controlledtrial.BJD2011;164:163-169

13. Boer and Nazary – Long-term results ofacitratin therapy for hidradenitis supperativa. Isacne inversa also a misnomer?BJD2011;164:170-175

14. Lepping et al – Delusional Infestation indermatology in the UK: prevalence, treatmentstrategies, and feasibility of a randomisedcontrolled trial.CED2010;35:841-844.

Abbreviated Prescribing Information for Dovobet® 50 microgram/g + 0.5 mg/g gel. Indications: Topical treatment of scalp psoriasis in adults. Topical treatment of mild to moderate ‘non-scalp’ plaque psoriasis vulgaris in adults. Active ingredients: 50 µg/g calcipotriol (as monohydrate) and 0.5 mg/g betamethasone (as dipropionate). Dosage and Administration: Apply to affected areas once daily. Recommended treatment period is 4 weeks for scalp and 8 weeks for ‘non-scalp’ areas. If it is necessary to continue or restart treatment after this period, treatment should be continued after medical review and under regular medical supervision. When using calcipotriol containing medicinal products the maximum dose should not exceed 15g/day. Treated area should not exceed 30% of body surface. Safety and efficacy in children under 18 years have not been established. Safety and efficacy in severe renal insufficiency or severe hepatic disorders have not been evaluated. Shake bottle before use. Do not apply directly to the face or eyes. Wash hands after use. It is not recommended to take a shower or bath, or to wash the hair in case of scalp application, immediately after application as the gel should remain on the skin during the night or day. If used on the scalp usually between 1g and 4g/day is sufficient for treatment. Contra-indications: Hypersensitivity to any constituents. Erythrodermic, exfoliative or pustular psoriasis. Patients with known calcium metabolism disorders. Viral skin lesions, fungal or bacterial skin infections, parasitic infections, skin manifestations in relation to tuberculosis or syphilis, perioral dermatitis, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, acne vulgaris, acne rosacea, rosacea, ulcers, wounds, perianal and genital pruritus. Precautions and Warnings: Avoid concurrent treatment with other steroids. Adrenocortical suppression or impact on the metabolic control of diabetes mellitus may occur. Avoid application on large areas of damaged skin, under occlusive dressings or on mucous membranes or skin folds. Do not use on the skin of the face or genitals. Avoid inadvertent transfer to face, mouth and eyes. Wash hands after applying. There may be a risk of generalised pustular psoriasis. With long-term use there is an increased risk of local and systemic corticosteroid adverse reactions in which case treatment should be discontinued. There may be a risk of rebound when discontinuing treatment. No experience of use in guttate psoriasis. No experience of concurrent use with other antipsoriatic products administered topically (to the

same treatment area) or systemically; or with phototherapy. Physicians are recommended to advise patients to limit or avoid excessive exposure to natural or artif icial sunlight. Use with UV radiation only if the physician and patient consider that the potential benefits outweigh the potential risks. Contains butylated hydroxytoluene which may cause local skin reactions or irritation to the eyes and mucous membranes. Use in Pregnancy and Lactation: Only use in pregnancy when potential benefit justifies potential risks. Caution when prescribed for women who breast-feed. Instruct patient not to use on breast when breast-feeding. Side Effects: Pruritus. Additional undesirable effects observed for calcipotriol and betamethasone: Calcipotriol: application site reactions, skin irritation, burning and stinging sensation, dry skin, erythema, rash, dermatitis, eczema, psoriasis aggravated, photosensitivity and hypersensitivity reactions including very rare cases of angioedema and facial oedema. Hypercalcaemia or hypercalciuria may appear very rarely. Betamethasone: local reactions, especially during prolonged application including skin atrophy, telangiectasia, striae, folliculitis, hypertrichosis, perioral dermatitis, allergic contact dermatitis, depigmentation, increase of intra-ocular pressure, cataract, colloid milia, generalised pustular psoriasis, infections. Systemic reactions occur more frequently when applied under occlusion, on skin folds, to large areas and long- term treatment. Legal Category: POM. Product Licence Number and Holder: 05293/0005 LEO Pharmaceutical Products Ltd. A/S, Ballerup, Denmark. Basic NHS Price: £36.50/60g, £67.79/2 x 60g. Last revised: November 2010. Further information can be found in the Summary of Product Characteristics or from: LEO Pharma, Longwick Road, Princes Risborough, Buckinghamshire, HP27 9RR. ® Registered Trademark. e-mail: Dovobet.UKenquiries@leo-pharma.com

Adverse events should be reported. Reporting forms and information can be found at www.yellowcard.gov.uk. Adverse events should also be reported to Drug Safety at LEO Pharma by calling 01844 347333.

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LEO® ©LEO Pharma, UK, All LEO trademarks mentioned belong to the LEO Group. Code: 1008/10888 February 2011