A presentation developed on behalf of the British Skin Foundation by: Dr Tim Cunliffe

1
A presentation developed on behalf of the British
Skin Foundation by Dr Tim Cunliffe
2
Acknowledgements

• We are extremely grateful to Steifel and Leo
  Pharma for an educational grant

3
Disclaimer

• Neither company, nor any other, had any influence
  in the content of the presentation
• Two of the authors (AL and WJC) have / had
  consultancies with several of the companies who
  make acne treatments

4
Contents of the presentation

• Information on the aetiology of acne
• Techniques for assessing acne
• Preferred treatment regimes
• Reasons for poor response

5
Aetiology of acne

• Androgen induced seborrhoea
• Comedone formation
• Colonisation of the pilosebaceous duct with P.
  acnes
• Production of inflammation

6
Is there a relationship between acne, hormones
and sebum production?

• YES
• Androgens Sebum production
• Anti Androgens Sebum production
• eg Dianette

7
There is a correlation between acne severity and
sebum excretion rate (SER) More sebum, more acne
2.0 1. 5 1.0 0. 5
SER µg/cm2/min
Controls Mild acne Moderate acne
Severe acne
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The evidence suggests that in most patients the
seborrhoea of acne is due to an increased
response of the sebaceous gland to normal levels
of plasma androgens

• What is the cause of the seborrhoea?

9
Significant endocrine disease can occasionally
cause acne

• Polycystic ovarian syndrome (PCOS) may present
  with
• Acne
• Irregular periods lt4 per year
• Hirsutism
• Female pattern alopecia
• Obesity
• If necessary, patients suspected of polycystic
  ovarian syndrome should be investigated

10
Investigations for PCOS

• Perform the tests in the luteal phase
• Between 9-10am
• Testosterone
• SHBG
• DHEA
• Prolactin
• LH / FSH ratio
• Such tests are expensive and not needed for the
  average acne patient

11
Other endocrine diseases can very occasionally
cause acne

• For example it might be worthy of excluding late
  onset congenital adrenal hyperplasia and
  Cushings syndrome in poor responding patients,
  by testing for
• -17 alpha hydroxy progesterone and cortisol
• - Dexamethasone suppression test
• Such tests are expensive and not needed for the
  average acne patient

12
Comedones are a central feature of acne and
present as

• Blackheads
• Whiteheads
• Microcomedo (this is the histological precursor
  of a clinical comedone)

13
Microbial colonisation

• Microbial colonisation occurs later in the
  development of acne lesions
• The seborrhoea and comedo formation alter the
  ductal micro environment which results in
  colonisation of the duct with P. acnes
• P. acnes are the most important organisms

14
Inflammation

• Is often the sign that triggers a patient to see
  a doctor

15
Summary of the aetiology of acne
Androgens
Seborrhoea
Comedo formation
Changes in the ductal micro environment result in
P. acnes (ductal) colonisation
Inflammation
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The choice of acne therapy should be based on the
following facts

• 1. A sound knowledge of the aetiology of acne
  this can help target aetiological factors
• 2. An adequate assessment of the severity of the
  disease
• 3. Discussions with the patient about the disease
  and ways of optimising compliance with therapy

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1.Actions of Anti-Acne Therapies

• Topical retinoids
• Normalizes ductal
• desquamation
• Reduces inflammatory response

• Oral Isotretinoin
• Reduces sebum
• Normalizes ductal desquamation
• Inhibits P acnes growth
• Reduces inflammatory response

• Antibiotics
• Inhibit P Acnes
• Reduce inflammation

• Hormones
• Reduce sebum production
• Reduce comedones

• Benzoyl peroxide
• Inhibits P Acnes
• Reduces
• inflammation

also reduce comedones
18
2.Why is assessment of Acnenecessary?

• To evaluate overall severity
• To help to select appropriate treatment
• To measure treatment response
• To estimate patient satisfaction

19
Which factors contribute to the overall
assessment of acne severity?

• The patients history
• The clinical appearances
• The psychosocial effects of the disease

20
Useful clues can be obtained from the history,
for example

• Mature acne
• produces greater psychosocial problems than in
  younger acne patients with a similar level of
  acne
• Duration of acne
• the greater the duration of acne the greater the
  likelihood of despondency and poor compliance
• Family history
• severe acne and persistent acne may have a
  genetic predisposition

21
Other important facts which can be obtained from
the history

• Menstrual cycle
• premenstrual flare occurs in 70 of females
• Previous treatments and response
• unsuccessful therapies produce despondency
• Poor Compliance
• produces poor clinical outcome
• Adverse effects of therapy
• will affect outcome and compliance

22
Acne assessment

• Physical assessment of acne severity is
  necessary methods include
• The use of comparative pictures, as demonstrated
  in the next series of pictures
• Consider individual patient pictures
• digital camera
• Consider patients perception
• This is most important
• one useful method is to utilise a visual analogue
  scale

23
It is important to assess the lesion types

• Different treatment types will influence acne
  therapy
• - for example, comedones necessitate topical
  retinoids
• Post inflammatory pigmentation and scarring also
  contribute to the over all acne severity

24
It is necessary to Assess the Psychosocial impact
of the disease

• Acne can produce
• Anxiety
• Depression
• Low esteem
• Poor interpersonal relationships

25
Acne severity seen by the physician does not
necessarily correlate to how the patient feels

• Some patients with mild physical disease may be
  significantly affected by the disease
• Mature acne patients are disproportionately
  affected by the disease
• Therefore consider using one of the validated
  assessment questionnaires which are fairly easy
  to use and only take a few minutes to complete

26
Do not forget to discuss the following issues
with the patient

• The cause of acne
• Physiological factors which influence acne
• Potential treatments and their side-effects
• Compliance with therapy

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Physiological factors which may influence acne

• Acne is frequently worse premenstrually
• Sunshine temporarily helps
• Stress may aggravate the problem in such
  circumstances the spots may be picked
• Diet recent evidence indicates that eating a non
  westernised diet may be associated with little or
  no acne

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Why could such a diet influence acne?

• Simple carbohydrate foods, such as highly refined
  sugars, cakes bread etc which are quickly broken
  down during digestion are rapidly absorbed into
  the bloodstream producing what is called a high
  glycaemic index
• This stimulates insulin production
• This influences androgen metabolism
• Consequently may influence acne
• Thus a restriction in refined carbohydrates may
  be of help refined carbohydrates are virtually
  absent in certain non westernised diet
• There is the need for more research on this
  topic.
• The following website is helpful
• www.verity-pcos.co.uk

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Thus you now have a tick list for assessing acne
severity this should help to optimise treatment

• Overall physical severity
• Lesion type
• Sites affected
• Post inflammatory pigmentation
• Seborrhoea
• Scars
• Psychosocial effects

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At this stage the physician should be able to
classify acne as being

• Mild
• Moderate
• Severe

Comedonal Inflammatory
This allows a logical treatment choice for acne
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1st choice is usually topical retinoids

• Adapalene
• Isotretinoin
• Tretinoin
• Preferable to use in an evening
• Note topical therapy is less easy to apply to
  the back than to other sites

32
Alternative choices for predominantly comedonal
acne

• An alternative retinoid
• or
• Azelaic acid
• or
• 1-2 Salicylic acid

33

1st Choice for mild papular-pustular acne is
usually topical retinoids and anti microbials

• Topical retinoids
• Adapalene
• Isotretinoin
• Tretinoin

• Topical antimicrobials
• Benzoyl peroxide
• Clindamycin
• erythromycin
• Zinc erythromycin
• BP clindamycin
• BP erythromycin
• tetracycline

There are several papers confirming the benefit
of such combination therapies
34
Choice is usually oral antibiotics and
appropriate topical therapy

• First Choice of oral antibiotics is often
  oxytetracycline 500mg bd
• However for optimum absorption oxytetracycline is
  best taken ½-1 hour either side of food
• Fitting around lifestyles of patients can be
  difficult and so compliance issues may result
• So what are the alternatives?

35
Alternative oral antibiotics

• Tetracyclines
• Doxycycline (Vibramycin) 100mg daily
• Lymecycline (Tetralysal 300) 408mg daily
• Minocycline (Minocin MR) 100mg daily
• More expensive and more side-effects than other
  antibiotics
• Macrolides
• Erythromycin 500mg bd

36
Which topical therapies can be prescribed with
oral antibiotics?

• Topical retinoids
• Topical antimicrobials (benzoyl peroxide,
  antibiotics, azelaic acid)
• Topical nicotinamide.
• It is probably best not to prescribe dissimilar
  oral and topical antibiotics

37
Is there any value in prescribing combined
topical and oral therapy?

• This prescribing habit has been a feature of acne
  therapy for many years
• Several studies support this therapeutic concept

38
Alternative oral treatment for females with more
severe acne

• Dianette plus appropriate topical treatment
• a topical retinoid topical benzoyl
  peroxide/antibiotic/combination therapies

39
When to use hormonal therapy

• In female patients with moderately severe acne
  requiring
• acne therapy
• menstrual cycle regulation
• oral contraception
• treatment of significant endocrine disease such
  as PCOS

40
A frequently asked question is, which drugs can
be used during pregnancy

• The following are usually regarded as being safe
  should the physician and patient feel it
  necessary to prescribe during pregnancy
• 5 Benzoyl Peroxide
• 2 Topical erythromycin
• Oral erythromycin, 500mg b.d
• Please check carefully with up-to-date
  information before prescribing

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What is severe acne?

• Severity is a combination of
• physical appearance
• psychological factors
• Post inflammatory pigmentation
• scarring

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Usual treatment of severe acne

• Oral isotretinoin
• High dose oral antibiotics/cyproterone acetate
• minocycline (100mgs bd)
• trimethoprim (300 mg bd)
• Dianette cyproterone acetate (50-100 mg/10
  days)
• appropriate topical therapies
• Short courses of oral corticosteroids are often
  required
• Such therapies should only be prescribed by the
  dermatologist or an experienced general
  practitioner working in a dermatological clinic

43

• It is not the purpose of this presentation to
  discuss therapy with oral isotretinoin in any
  detail

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What is the optimum duration of acne therapy
(excluding oral isotretinion)?

• Topical therapy will probably be needed for the
  entire duration of the patients disease
• Oral therapy is often prescribed for somewhere
  between 4 and 12 months, sometime shorter,
  sometimes longer
• Therefore on stopping oral therapy, continued
  therapy with topical therapy is required
• Reasonable topical options include a retinoid in
  the evening and in the morning, benzoyl peroxide,
  a topical antibiotic or a combination therapy

45
Some people dont respond adequately. WHY?

• Poor compliance
• Side effects
• P. acnes resistance
• relevant for 10-20 of patients
• Wrong diagnosis
• Severe acne variants

What is the expected response in the average
patient?
46
Data showing the expected Response(excluding oral
isotretinoin)
80 60 40 20
improvement
1 2 4 8
Time (Months)
47
Poor compliance is a major reason for poor
response

• 18 week period compliance rates
• With topical therapy 38
• With oral therapy 45
• this data is based from data derived both in
  general practice and hospital compliance with
  oral isotretinoin is significantly greater

48
The following factors are associated with poor
compliance

• Smoking
• Alcohol
• Psychosocial impairment
• Second or subsequent courses of oral isotretinoin

49
Side-effects from topical therapy can be a reason
for a poor response

• Contact irritant dermatitis is very common
• How to combat irritation
• Use less irritant products such as the newer
  formulations
• Oil free moisturiser
• Use hydrocortisone cream twice daily, if
  necessary for 5-7 days
• Reintroduce the acne therapy gradually

50
Common side effects of oral therapy

• Oral antibiotics
• Gastrointestinal (diarrhoea, colic, dyspepsia)
• Vaginal candidiasis
• Dianette
• It is recommended that the Dianette should be
  stopped 3-4 months after disease is under control

51
Uncommon side effects of oral therapy

• Doxycycline
• Light sensitive rash
• Minocycline
• Lupus Erythematosus
• Benign intracranial hypertension
• Pigmentation
• Check LFTs, ANA and p. ANCA every 3-4 months

52
There are many side effects of oral isotretinoin
and include

• Dry skin, especially on the face
• Cheilitis
• Headaches
• Teratogenicity
• Adverse psychiatric effects
• Mood swings and Depression
• adequate contraception is necessary whilst on
  the drug and for 4 weeks before and 4 weeks after
  discontinuing therapy. Please consult with the
  BAD and the manufacturers for updated
  recommendations
• it is necessary to discuss these issues with
  the patient and where appropriate, with the
  family and friends

53
Propionibacterium acnes resistance

• This is an increasing problem worldwide
• Laboratory detection is of the order of 60
  especially with erythromycin and clindamycin
• In clinical practice it probably explains the
  poor response in about 15 -20 of patients

54
When to suspect such resistance

• In patients who have received many oral and or
  topical antibiotics
• In patients who were doing well and are now
  responding badly

55
Treatment and prevention of P. acnes resistance

• Minimise the use of antibiotics-but we do have to
  practice in the real world!
• When possible use treatments which are not
  antibiotics such as
• Retinoids topical and oral
• benzoyl peroxide
• azelaic acid
• Dianette

56
Failure to remember the usefulness of physical
treatment may result in an inadequate response

• Do not forget
• Comedone extraction
• Intralesional triamcinolone
• To a large, recently developed, nodule
• UV therapy
• Cryotherapy
• To a large, old nodule
• Several new light therapies seem promising for
  the future

57
Light therapy can also be considered but few
adequate trials have been performed, for example
with

• Blue light (415 nm)
• Blue and red light (415nm 660nm)

58
Light therapy also includes the following
procedures

• Clear light
• Nlite
• Photo dynamic therapy
• such as the application of aminolaevulinic acid
  for 4 hours followed by irradiation of the skin
  with either broadband light or polychromatic
  visible light
• These are areas of ongoing research

59
Certain subtypes of acne may produce clinical
failure

• Sandpaper acne
• Macrocomedones
• Severe acne variants
• acne fulminans
• acne conglobata
• not discussed in this presentation

60
Sandpaper acne

• Multiple small whiteheads
• Frequently produce superficial inflammation
• Skin rough to feel, like sandpaper

61
Treatment of sandpaper acne

• Can be difficult
• Rarely responds well to antibiotics and topical
  retinoids
• Best therapy is usually oral isotretinoin (0.5
  mg/kg/daily) for four months

62
Macrocomedones may produce

• Considerable cosmetic difficulties
• Significant inflammation
• Significant inflammation if the patient is
  inappropriately prescribed oral isotretinoin

63
Macrocomedones may produce significant
inflammation whilst taking oral isotretinoin

• This next patient had virtually no lesions on the
  neck until 2-3 weeks of taking oral isotretinoin
  the macrocomedones flared into significant
  nodules
• The reason for this flare is that when on oral
  isotretinoin the P. acnes die, resulting in the
  release of many inflammatory mediators

64
Treatment of macrocomedones

• Apply a local anaesthetic cream under occlusion,
  for about 1.25 hrs, then
• Perform gentle cautery the heat should be
  sufficient to char paper towelling
• Hyfrecation is an alternative (but less
  effective)
• If the patient is taking oral isotretinoin then
  such therapy should be stopped / reduced for 1
  2 weeks if the acne has flared badly
• Oral corticosteroids will frequently be required
  if there is much inflammation, for 1- 3 weeks

65
Complications of gentle cautery are very uncommon

• Scarring
• Increased or decreased pigmentation
• Obviously caution is required in dark skin
• If in any doubt, or if the area to be treated is
  extensive, or if the patient is dark skinned,then
  try on a test area
• The aim of the treatment is not to destroy the
  macrocomedones but to encourage an influx of
  polymorphonucleocytes into the lesion

66
Significant inflammatory disease will produce a
poor response

• for example, sinus tract disease
• This is where large nodules fuse together and
  produce extensive inflammation with inevitable
  scarring

67
Conclusion 1

• Therapy should be based
• On a knowledge of the aetiology of acne
• On good evidence
• Less so on opinion
• On a detailed discussion with the patient

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Conclusion 2Acne treatments should aim to reduce

• Seborrhoea
• Comedones
• P. acnes
• Inflammation
• possibly the earliest features of acne

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Conclusion 3Acne assessment and a good history
are essential parts of management and should
include amongst other items, information on

• Family history
• Failure of previous treatment
• Physical appearance, as assessed
• By the patient
• By the assessor
• Socio-psychological effect
• Duration of the disease

70
Conclusion 4

• Attention to all these aspects of acne should
  help to optimise a successful outcome
• However there are a group of patients who still
  do not respond well or relapse very quickly on
  stopping treatment
• There is therefore a need for more basic and
  clinical research to help improve the risk
  benefit ratio

71
And finally something about the British Skin
Foundation
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British Skin Foundation

• A unique charity raising and distributing money
  for research into skin disease
• Administered by the British Association of
  Dermatologists
• Every pound we raise is spent on quality, peer
  reviewed research!
• We need your help, please.

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British Skin Foundation

• How can you help ?
• by gift aiding on an annual basis
• by helping in departmental / BSF events to raise
  money and most importantly to raise our profile
  to the public

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British Skin Foundation

• We do hope that you can help.
• We invite you to apply for funding
• We are always very happy to hear your ideas and
  comments
• Our telephone number is 020 7391 6349
• Website is www.britishskinfoundation.org.uk
• Thank you