Identifying and Managing Acne

What is Acne?

Acne is one of the commonest inflammatory skin disorders and therefore represents a very important skin disease. The mildest form is known as “physiological” acne embracing just a few perceivable blackheads and or occasional red spots; most of the adolescent population will suffer from this form at some time.

Of the 70-87% of adolescents who develop acne, 15 - 30% will seek medical advice. Many subjects seek advice from the pharmacist, but some will not seek help at all because of embarrassment or the misconception that no treatment is available. In some cases scars will ensue: 2-7% of patients develop life-long scars emphasising the importance of effective treatment. Many patients also suffer from significant psycho-social disability.

Acne represents a disease of the hair and sebaceous follicles known collaboratively as the “pilosebaceous units” present on the face and upper trunk. These follicles are under the influence of hormones called androgens. As a consequence of the hormonal drive, acne typically begins at puberty or in early adolescence, reaching peak incidence and severity in both sexes between the ages of 16 and 20 years.

Acne is a chronic disease, lasting in many cases until the mid-20s. In 7% of subjects clinical acne persists until 40 - 50 years of age - this is more common in females. Rarely, acne occurs in infancy.

How Does Acne Develop?

In the skin there are three sorts of follicles; vellus follicles, the hair follicles and the sebaceous (grease) follicles. It is the sebaceous follicles which are involved in acne. These sebaceous glands occur predominantly on the face, back and chest.

There are four main factors involved in the development of acne:

Increased production of the greasy product sebum. This is under the control of androgen hormones which result in increased grease production known as “seborrhea”.
Increased cell turnover in the duct of the pilosebaceous unit known as ductal “hyperkeratinisation”. This results in the formation of comedones more commonly know as blackheads and whiteheads.
The build up (colonisation) of acne bacteria called Propionibacterium acnes (P. acnes) in the duct.
The development of inflammation – this is both an early event in the evolution of acne and occurs later as a result of P.acnes colonizing the duct which results in a number of immune reactions in the skin which result in inflammation and the red spots recognized in acne.

Sebum Production

The cells at the edge of the sebaceous (grease) glands divide and produce lipids (fats) in abundance. As these cells move further towards the sebaceous duct they breakdown, resulting in the liberation of the greasy material called “sebum” which passes into the sebaceous ducts and onto the skin surface. Skin surface levels of sebum can be measured readily. It has been clearly demonstrated that patients with acne produce more sebum than those with little or no acne and the level of sebum production correlates to acne severity.

Although the sebum (grease) production is dependent on hormones, most acne patients have normal hormone levels. However, if a patient with acne has very irregular periods, excess facial hair (hirsutism) or scalp hair loss (female pattern androgenic alopecia) it is important to consider whether there is an associated disorder like polycystic ovarian syndrome (PCOS) or late-onset congenital adrenal hyperplasia.

Comedome Formations (blackhead and whiteheads)

Comedones are seen in the skin as blackheads and whiteheads - but these lesions are preceded by the microcomedo. The microcomedo is only seen under the microscope not with the naked eye. If a skin sample [a biopsy] is taken from normal-looking skin in a patient with acne, it will reveal a microcomedo in 30% of subjects. This is important as the microcomedo represents the precursor to both the red inflamed spots we recognize in acne, and the non inflamed blackheads and whiteheads.

Treatments for acne should therefore be aimed at reducing or clearing the microcomedo in an attempt to prevent the development of clinically apparent non inflammatory and inflammatory lesions.

Topical retinoids are regarded as the treatment of choice and should be applied to all areas of skin affected by acne even in the normal looking areas in an attempt to clear the microcomedones before the visible acne lesions emerge.

Comedone formation results from cells called corneocytes accumulating in the duct of the pilosebaceous unit. It has been suggested that the corneocytes fail to separate adequately and move into the lumen of the duct, and are subsequently sloughed onto the skin surface.

It is not known why some abnormal follicles develop into whiteheads or blackheads. A whitehead is referred to as a closed comedone because it has a very small exit onto the skin surface. The contents within the duct of a whitehead are easily retained at this site. These contents contain many substances that can result in inflammation.

In contrast, a blackhead has an exit onto the skin surface which is relatively large. A blackhead is therefore frequently referred to as an open comedone. Whiteheads are much more prone to develop into inflammatory lesions than are blackheads.

The stimulus for ductal hyperkeratinisation is complex and involves stimulation from androgens, sebum composition and locally produced chemicals called cytokines.

The Role of Acne Bacteria in Acne

Acne is not infectious. Propinibacteria acnes (P.acnes) are present on all sebaceous-rich areas from early adolescence until old age. Skin surface numbers of P. acnes are similar in patients with and without acne.

However, we know that most healthy looking follicles in acne patients are not colonized with p.acnes but that most follicles in adults without acne are colonized. Colonisation of the pilosebaceous duct with P. acnes is important for the development of inflamed lesions and is likely to occur early after comedone formation. Just how P. acnes colonise the duct is not known. As P. acnes are not motile, colonisation of the duct is likely to relate to the specific environment of the acne-prone follicles. In addition, variation in the environment within the duct will result in variable production of chemicals from the bacteria able to trigger inflammation. Evidence supporting this theory includes the variable pH of 2-8 noted within comedones. This variation will markedly effect the growth of bacteria within these lesions.

How Does Acne Present?

Examination of patients with acne will reveal:

Seborrhoea (greasiness); early onset and excess sebum production relate to the subsequent acne severity.
Comedones; known as whiteheads and blackheads.
Superficial inflamed lesions (papules, pustules and macules, which represent late-stage resolution of inflammatory lesions)
Deep inflamed lesions (nodules and deep pustules) Scars (atrophic, ice-pick, macular, keloid, hypertrophic scars and perifollicular ealstolysis)
Post-inflammatory pigmentation is a very common feature in patients with dark skin. It is also a very persistent problem and may prove very difficult to treat.

Acne and the possible scarring that can ensue may cause significant psycho-social disability. The severity of the disease does not necessarily correlate with the psycho-social morbidity.

What Other Conditions Look Like Acne?

Rarely acne can be misdiagnosed. Confusion may arise with the following disorders:-

Perioral/dermatitis
embraces small itchy papules around the mouth or eyes made worse with topical corticosteroids but responds well to a four-month course of an oral tetracycline

Seborrhoeic eczema
represents a somewhat itchy, dry scaling skin rash with diffuse erythema often associated with similar problems on the scalp or upper trunk

Rosacea
Usually rosacea has an older age of onset, there is usually a background of redness and broken blood vessels in the skin and rare involvement other than the face. No comedones or scars are seen, flushing is common and eye problems may be associated. Rosacea can be made worse with topical corticosteroids.

Pomade acne
May occur in association with ordinary acne in patients using pomades and hair gels. Stopping these cosmetic preparations along with topical retinoid usage usually resolves the problem.

Steroid-induced acne

May occur from the excessive use of topical steroids and may occur from long-term oral steroids. The lesions are more mono-morphic than in ordinary acne.

How Do We Treat Acne?

Treatment should be aimed at reducing the main causative factors - therefore a combination of therapies is usually required. Patient expectations and their ability to use/take their prescribed therapy will significantly effect compliance. The following should be considered:

acne is a chronic disease
a treatment strategy is needed and it is likely that long-term therapy will be required
acne is a slow-responding disorder with little improvement in the first 3 - 5 weeks
there is a need for continued compliance
certain physiological events may influence acne, for example

Other considerations:

stress may make acne worse
diet has not currently been shown to aggravate acne although there are reports to suggest that patients with polycystic ovary syndrome and acne will improve if they can lose weight. Other studies have recently indicated there may be a link between milk and acne. As a result of these reports there is currently renewed interest in the link between diet and acne.
studies have indicated that there may be a link between genetics and acne and also possibly a relationship between the susceptibility to scar and family history.
some reports have indicated that smoking can make acne worse
a premenstrual flare is common in 70% of females
sunshine often helps acne but only temporarily
humidity can trigger acne
certain cosmetics can be comedogenic i.e. encourage the development of blackheads and whiteheads, these should be avoided

Choice of Topical Treatment

Topical therapies are used in the following circumstances:

in mild disease
in combination with oral antibiotics in moderate disease
in combination with hormonal therapies in females
as a maintenance therapy after oral therapy has been discontinued

The choice of topical therapy may be dictated by the type of acne lesions. Comedolytic agents are those that reduce comedones, a topical retinoid is the most effective treatment for this although benzoyl peroxide has some mild impact in this context. Comedogenic agents prevent microcomedones developing, topical retinoids are the only agents that have been shown to do this. Anti-inflammatory agents include novel topical retinoids, non-antibiotic antimicrobials such as benzoyl peroxide and antibiotics.

Although there have been many clinical trials performed in acne patients very few have been well conducted. As the microcomedo precedes both non inflammatory and inflammatory lesions topical retinoids should be considered as first line therapy in most patients. The novel retinoids are less irritant than the older formulations of all - trans retinoic acid and are less likely to result in early treatment flare following the start of therapy. If the disease is mild but with a significant number of inflamed lesions then benzoyl peroxide, or a topical antibiotic should be combined with the topical retinoid.

Choice of Therapy for Moderate to Severe Acne

Extent and activity of acne, degree of grease production (seborrhoea), the psychosocial impact of disease, the presence or risk of scarring and the impact of previous treatment should all be taken into account when considering the “severity” of acne. Treatment choices include oral antibiotics and hormonal treatment (for females e.g. Dianette and Yasmin) and oral isotretinoin in more severe disease. Dianette has a product licence for severe acne but is not licensed as an oral contraceptive in the UK. Isotretinoin has been available from the early 1980s for the treatment of severe acne and works extremely well in acne as it is the only therapy which impacts on the main factors implicated in acne.

It reduces sebum excretion, by 90% as early as six weeks of treatment
It also reduces comedones by 90 percent at about three months of treatment
It has no direct effect on the P. acnes but indirectly alters the micro- environment of the intra-follicular duct. By this mechanism it reduces P. acnes numbers very effectively
It has a direct anti-inflammatory effect.

The prescribed adult dose should start at 0.5 mg/kg/day and should be titrated up to 1 mg/kg/day according to tolerance and response. Duration of therapy will depend on dosing and response. In most patients, benefit is considerable with many having achieved almost 100 percent improvement at the end of treatment. The rate of relapse post-therapy varies, but it is somewhere in the order of 30 - 70% and depends upon daily dose, duration of therapy, age of patient, site of acne (trunal acne in males relapsing more frequently), sebum excretion and initial acne severity.

Side-effects of oral isotretinoin -There are many side effects of oral isotretinoin:

Drying effects are very common and usually resolve with moisturisers:

Cheilitis. – drying and cracking of the lips. The regular use of lip salve / moisturizer is usually required
Facial dermatitis - this very common side-effect requires the use of moisturisers on a regular basis
Dermatitis elsewhere - quite common and requiring the use of moisturisers
Nasal crusting - quite common, may be associated with nose bleeding
Conjunctivitis is quite common, and may require false tears as lubrication
Secondary infection with Staphylococcal aureus is quite common at all the above sites, requiring either the addition of local or oral antibiotics.
There are also many uncommon side-effects such as skin fragility (patients should be warned to avoid wax epilation), pyogenic granulomata, and excessive sweating.

Systemic side-effects

Oral isotretinoin is markedly teratogenic this means it can damage an unborn baby so it is imperative that ladies of child bearing age do not take isotretinoin without careful explanation and it is mandatory that they avoid getting pregnant whilst taking the medication and for 5 weeks afterwards. A pre-therapy pregnancy test is required on the first, second or third day of the period. The therapy should then be started, if the test is negative, on the same day that the sample is taken.
The drug is associated with significant adverse psychiatric events in a small number of patients - in particular mood swings and depression. Rarely, suicide has been reported. These events must be discussed with the patient and preferably with the family. As with the pregnancy issues we ask our patients to sign a form which indicates that we have discussed potential adverse psychiatric events with them.
Headaches occur quite frequently but rarely necessitate stopping therapy. Oral paracetamol usually controls the headaches should analgesia be required.
In a small number of patients myalgia (aching muscles) and arthralgia (aching joints) may occur, this is more common in those that do a lot of sport. Paracetamol or a non-steroidal anti-inflammatory usually control the problem well.
Many other systemic side-effects have been recorded, including night blindness. There are a number of relevant articles on these issues in the literature.

Summary of Treatment Principles:

General principles - acne is a chronic, slow-responding disorder requiring good patient compliance
Topical therapy should include a topical retinoid
Topical therapy is required in most acne patients, either alone or in combination with oral antibiotics or oral contraceptives in females if not contra-indicated
Many topical agents produce redness and dryness and ahouls be combined with non oil based moisturisers
Systemic therapies include oral antibiotics. Tetracyclines should be the first-line choice and second generation tetracyclines are now considered the best choice due to less adverse effects and improved efficacy.
Oral contraceptives e.g. Dianette / Yasmin can be considered in females with severe acne
Patient management should include means of assessing the psychosocial impact of the disease
Severe acne may require oral isotretinoin which should be prescribed and managed by an experienced dermatologist.

Physical Treatments

This includes the following treatments:

the removal of blackheads using a blackhead remover
aspiration of and injection of the steroid triamcinolone into new cysts
cryotherapy (liquid nitrogen) of acne cysts
glycolic acid treatments - as available from many beauty therapists - are probably of no benefit in treating comedones and scars
lasers and light therapies – some studies are looking promising but there is still not consensus on the optimum system and to date the improvements achieved are not long lasting

These procedures require experience acquired in a dermatology clinic.

How Do We Treat Acne Scars?

The treatment of acne scarring is difficult. General practitioners may be able to prescribe therapies which influence the bulky scars that can develop called hypertrophic or keloids scars but they have little or nothing to offer the patient with scars resulting from loss of tissue i.e. atrophic or icepick scars.

Treatment of hypertrophic/keloid scars

1. Silicon gels are available from pharmacies without prescription. They are expensive and treatment for many months is required.
2. Occlusive therapy with the steroid tape Flurandrenolone (Haelan) applied over night may help to soften and flatten lesions. This is available on prescription.
3. Potent topical corticosteroids such as Dermovate cream applied very sparingly once to twice daily to the scar over three months may be of benefit in some patients. Great care must be taken to avoid the steroid coming into contact with surrounding normal skin as this could result in thinning of the normal skin.
4. Intradermal injections of the steroid triamcinolone given at monthly intervals may also help, but it is important that this is given be an experiences technician to avoid adverse effects including thinning of the skin.
5. Surgical removal of keloid/hypertrophic scar tissue is almost certain to result in further scarring so this approach should be adopted with great caution.
6. Cryotherapy (liquid nitrogen) may be partially effective but should be done by an experienced technician.
7. X-ray therapy has been reported as successful in some cases.
8. Laser treatment has also been utilized with minimal success. Several dermatologists around the UK carry out laser therapy for atrophic and ice-pick scars, but this procedure is rarely available on the NHS. It is expensive and results are variable.
9. There are reports of combined therapy with surgical excision, cryotherapy X-ray treatment and intralesional steroids.

Conclusions

Acne is a common disease of the pilo-sebaceous ducts
Androgen hormones drive the seborrhoea and play a role in comedone formation
Colonisation of the duct with P. acnes stimulates the production of inflammation
Acne patients are not endocrine or immunological misfits
Acne usually develops in early or late adolescence
Acne severity and prevalence peaks at 18 - 20 years
Acne usually resolves at the age of about 25 years
However, acne persists in 7% of patients up to the age of 45 years
The clinical features are seborrhoea, comedones (whiteheads, blackheads) superficial and deep inflamed lesions. Scarring may follow.
Treatment is aimed at the underlying processes involved in acne including increased grease production, development of blackheads and whiteheads, reduction in p.acnes bacteria and reduction in inflammation.
Many topical therapies result in dryness and irritation and should be combined with appropriate cosmetics to relieve any clinical symptoms and signs and should be selected as non-comedo