Acne vulgaris
NOTES
Introduction
       Acne vulgaris is a common chronic dermatological
       condition resulting from inflammation of the
       pilosebaceous unit.
Acne vulgaris is extremely common in adolescence affecting up to
95% of young people. Though in most cases it is relatively mild, up
to 1/3 have moderate or severe disease. It results in comedones
and inflammatory lesions that typically affect the face, chest and
back.
Beyond (and secondary to) its dermatological manifestations it can
have a profound impact on self-esteem and mental wellbeing.
Most cases respond to topical and/or oral therapies (e.g. antibiotics
and retinoids). Specialist dermatological and mental health
support can be required.
Epidemiology
        20-35% of adolescents are affected by moderate or
        severe acne vulgaris in western countries.
It is predominantly a condition of adolescents and young adults
affecting up to 95%. It is estimated that 85% of patients are aged
12-24, 8% 25-34 and 3% 35-44.
It affects males more than females in adolescence but becomes
more common in females in adulthood.
Pathogenesis
       Acne vulgaris is an inflammatory disorder affecting
       the pilosebaceous unit.
The pilosebaceous unit refers to the hair follicle, hair shaft,
arrector pili muscle and sebaceous gland. It is thought that
blockage and inflammation of these units leads to acne vulgaris.
Acne vulgaris is thought to result from the complex interplay of
numerous factors. The condition is characterised by:
   • Non-inflammatory comedones
   • Inflammatory papules, pustules and nodules
These lesions are thought to arise from precursor lesions termed
microcomedo. Factors thought to lead to the development of acne
vulgaris include:
   • Altered keratinocyte proliferation
   • Increased sebum production secondary to androgens
   • Bacteria (cutibacterium acnes formerly propionibacterium
     acnes)
   • Inflammation of the pilosebaceous unit
Insulin resistance, stress and skin trauma have all been identified
as possible risk factors. There is a great deal of interest in the
relationship between acne vulgaris and diet though research is
ongoing.
Clinical features
      Acne vulgaris is characterised by inflammatory and non-
      inflammatory lesions that typically affects the face,
      chest and back.
As described above, acne vulgaris is characterised by
inflammatory and non-inflammatory lesions:
   • Non-inflammatory comedones: closed comedones, often
     called whiteheads, are plugged follicles whilst open
     comedones, often called blackheads, are follicles with dilated
     openings (which allow oxidisation of follicle content resulting
     in a black colour).
   • Inflammatory papules, pustules, nodules and cysts:
     papules and pustules are superficial, small raised lesions less
     than 5mm in size. Nodules and cysts are deeper, larger
     lesions (>5mm) that may be fluctuant.
These lesions tend to be located in areas with a lot of
pilosebaceous glands - as such acne vulgaris typically affects the
face, chest and back. In darker skin lesions can be less apparent
as the erythema that surrounds lesions may be less obvious.
In chronic disease, skin may be affected by scarring due to the
healing of lesions. Post-inflammatory depigmentation and
hyperpigmentation of affected skin may occur.
                          Acne vulgaris
        Image courtesy of DermNet, Creative Commons licence
Acne conglobata
Acne conglobata is a rare and severe form of acne characterised
by inflammatory nodulocystic disease with interconnecting sinuses
and abscesses. It most commonly affects men between the ages
of 18 and 30. Severe scarring may occur.
Its development is thought to be related to the bacteria
cutibacterium acnes. It may also result from steroid use/abuse or
androgen-producing tumours.
Acne fulminans
Acne fulminans is defined differently in various texts but NICE
(NICE NG 198) describes it as a severe form of acne conglobata
with systemic features such a fever, arthralgia and
lymphadenopathy. It is rare and again typically affects young
males.
Patients with this condition should be urgently referred to the local
on-call dermatology team for same-day assessment.
Severity
       Classifying the severity of acne vulgaris can be helpful
       in guiding its management.
There is no single universal classification for the severity of acne
vulgaris. Severity can refer to the number and type of lesion
present or the impact on a person's health and well-being.
NICE guideline 198 (June 2021) describes severity based on the
lesions presents:
Mild to moderate acne includes people who have 1 or more of:
   • any number of non-inflammatory lesions (comedones)
   • up to 34 inflammatory lesions (with or without non-
     inflammatory lesions)
   • up to 2 nodules
Moderate to severe acne includes people who have either or both
of:
   • 35 or more inflammatory lesions (with or without non-
     inflammatory lesions)
  • 3 or more nodules
Management
      The management of acne vulgaris involves skincare
      advice, topical and oral therapies and support for
      any associated mental health disorder.
Skincare advice
NICE guideline 198 (June 2021) offers the following skincare
advice:
  • Advise people with acne to use a non-alkaline (skin pH neutral
    or slightly acidic) synthetic detergent (syndet) cleansing
    product twice daily on acne-prone skin.
  • Advise people with acne who use skincare products (for
    example, moisturisers) and sunscreens to avoid oil-based and
    comedogenic preparations.
  • Advise people with acne who use make-up to avoid oil-based
    and comedogenic products, and to remove make-up at the
    end of the day.
  • Advise people that persistent picking or scratching of acne
    lesions can increase the risk of scarring.
Medical therapy
There are a number of topical and oral treatments for acne
vulgaris. The options depend on patient factors, preference and
whether they are pregnant (or plan on getting pregnant) or
breastfeeding. The side effect profile of each treatment should be
considered and explained.
Patients should be advised that good adherence for several weeks
(typically at least 6-8 weeks) is needed before beneficial effects
are seen.
There are many options, here we give a brief outline of some of
the most commonly used medications:
  • Topical adapalene: a topical retinoid compound with anti-
    inflammatory effects. It is thought to reduce microcomedone
    formation.
  • Topical benzoyl peroxide: is a keratolytic medication that
    also has antibacterial effects. It reduces the amount of the
    bacteria cutibacterium acnes.
  • Topical tretinoin: has a combination of comedolytic and
    anti-inflammatory effects. It is also thought to reduce
    microcomedone formation.
  • Topical clindamycin: is a bacteriostatic antibiotic that is
    active against cutibacterium acnes. It also has anti-
    inflammatory properties.
  • Oral tetracyclines (doxycycline or lymecycline): are
    antibiotics that inhibit protein synthesis in bacteria.
For mild to moderate acne the following options should be
considered:
  • Topical adapalene with topical benzoyl peroxide:
    applied once daily in the evening. Cannot be used in
    pregnancy and caution is needed in breastfeeding. Side
    effects include skin irritation, burning sensation, bleaching (of
    hair and clothes) and photosensitivity.
  • Topical tretinoin with topical clindamycin: applied once
    daily in the evening. Cannot be used in pregnancy or in those
    breastfeeding. Can cause skin irritation and photosensitivity.
  • Topical benzoyl peroxide with topical clindamycin:
    applied once daily in the evening. Side effects include skin
    irritation, burning sensation, bleaching (of hair and clothes)
    and photosensitivity. It may be used with caution during
    pregnancy and breastfeeding.
For moderate to severe acne the following options should be
considered:
  • Topical adapalene with topical benzoyl peroxide:
    applied once daily in the evening. Cannot be used in
    pregnancy and caution is needed in breastfeeding. Side
    effects include skin irritation, burning sensation, bleaching (of
    hair and clothes) and photosensitivity.
  • Topical tretinoin with topical clindamycin: applied once
    daily in the evening. Cannot be used in pregnancy or in those
    breastfeeding. Can cause skin irritation and photosensitivity.
  • Topical adapalene with topical benzoyl peroxide plus
    either oral lymecycline or oral doxycycline: the topical
    medications are applied once daily in the evening with a
    once-daily oral antibiotic. Cannot be used in pregnancy or
    during breastfeeding. Tetracyclines are known to cause
    photosensitivity. Topical therapies may cause skin irritation,
    photosensitivity and bleaching. Cannot be used in under 12’s.
  • Topical azelaic acid plus either oral lymecycline or oral
    doxycycline: the topical azelaic acid is applied twice daily
    whilst the antibiotic is taken once daily. Cannot be used in
    pregnancy or during breastfeeding. Tetracyclines are known
    to cause photosensitivity. Cannot be used in under 12’s.
The effect of treatment should be reviewed at 12 weeks.
Generally, antibiotics should not be continued for longer than 6
months and should be stopped as early as possible.
If treatment has failed consider an alternative. In those with
moderate to severe disease who have not had a regimen with an
antibiotic, a regimen with an antibiotic should be considered. If
they have already been on antibiotics, referral to dermatology
should be made. In mild-moderate disease, referral should
generally be considered after two treatment regimens have failed.
Oral isotretinoin
Isotretinoin is derived from vitamin A and is a powerful anti-
inflammatory agent. It decreases sebum release and is thought to
lead to a reduction in bacteria in the skin. It has a number of
severe side effects and its use should be controlled by consultant
dermatologists.
Oral isotretinoin is reserved for those with severe disease not
responding to treatment and acne that is at risk of causing
permanent scarring. It is only used in those over the age of 12
after appropriate counseling and consideration of the risks.
Courses often last for 16-24 weeks.
NICE guideline 198 (June 2021) advises considering its use in
those over the age of 12 who have failed treatment with topical
therapies and systemic antibiotics. Examples include:
   • Nodulocystic acne
   • Acne conglobata
   • Acne fulminans
   • Acne at risk of permanent scarring
It may be given alongside a limited course of oral corticosteroids if
the oral isotretinoin causes an acute flare. Oral corticosteroids can
also be given at the onset of treatment in those with acne
fulminans to prevent an acute flare.
Oral isotretinoin is teratogenic. Patients must understand this and
follow the MHRA ‘Oral retinoid medicines: revised and simplified
pregnancy prevention educational materials for healthcare
professionals and women’.
It is also contraindicated in those with hypervitaminosis A,
hyperlipidaemia, liver dysfunction or allergies to any of its
constituents. It must be used with caution in those with renal
impairment, diabetes and dry-eye syndrome.
It is important to assess the psychological well-being of patients
both prior to and during therapy. There have been rare reports of
sudden and severe worsening of depressive symptoms and suicide
in those taking oral isotretinoin but a causal relationship is yet to
be formally established.
For more information see this MHRA guidance.
Referral
Specialist review should be sought in patients acne conglobata or
nodulocystic acne and where there is any diagnostic uncertainty.
Referral should also be considered in those not responding to
treatment, with scarring or with persistent pigment changes.
In those suffering with significant or persistent psychological
distress referral to both dermatology and mental health services
should be considered.
Complications
      Complications of acne vulgaris include permanent
      skin changes and effects on mental wellbeing.
Skin changes
Healing lesions can result in hypertrophic and/or atrophic scars.
Hyper and/or hypopigmentation may also occur.
Psychological impact
The psychological impact varies between patients. It can have a
significant effect on self-esteem often at a key time in a young
person's development. There is an increased risk of anxiety,
depression and suicide.
All patients should have their mental wellbeing checked, suicide
risk assessed and offered a contact point if they should need it.
This assessment should be repeated during their follow-up care.
Prognosis
       Acne vulgaris tends to resolve at the end of
       growth.
Treatment regimens are effective in reducing or eliminating
symptoms in many patients. The disease itself normally resolves
as the individual reaches maturity and enters adulthood.
Permanent scarring and/or pigment changes can occur.
A minority of patients are affected in adulthood, whilst others
develop late-onset disease.