Acne Vulgaris

Acne vulgaris, commonly referred to as acne, is a skin condition characterised by whiteheads, blackheads and inflamed red pimples. It is a very common skin condition in adolescents and affects a significant minority of adults. Acne can severely impact an individual’s psychological well-being, as acne can lead to scarring. Although not a systemic disease (i.e. acne is usually confined to the skin and does not affect other tissues or organs), a rare and systemic form of acne, acne fulminans, can affect bones and other tissues. Other variants of acne that are often severe exist, but these are rare in comparison with acne vulgaris. Unless indicated otherwise, the discussion in this article pertains to acute vulgaris.

Incidence

Acne affects 95 – 100% of adolescent boys and 83 – 85% of adolescent girls. Acne usually resolves before the age of 25 years. About 12% of women and 5% of men have acne at the age of 25 years. At 40 years of age, 1% of men and 5% of women have acne. Acne manifests in adulthood either for the first time or may recur in individuals who have had acne in adolescence.

It has been estimated that about 14% of affected individuals consult their general practitioners, while about 0.5% of individuals consult a dermatologist for their acne. Acne can occur in neonates and infants, predominantly in males, in the first year of life and can last up to four years. In females who develop acne earlier in life, there is an increased risk of developing more severe acne. Pre-menstrual flare-up of acne can occur in women.

Causes

The surface of the skin contains pores, each of which opens into a canal called a follicle. Each follicle contains a hair and an oil gland (sebaceous gland). The oil (sebum) from these glands lubricates the skin and helps remove dead skin cells. If too much sebum is produced, the pores may become blocked with the accumulation of dirt, debris and bacteria. The blockage is called a plug or a comedone. If these plugs rupture, the oil and bacteria can reach the surrounding vicinity, leading to inflammation. If the inflammation spreads deep down the skin, the pimples may enlarge to form cysts, which can be painful.

Acne can be caused (or exacerbated) by:

• Family history of acne (i.e. genetic factors): A strong genetic component is believed to be associated with acne. Family history of acne predisposes an individual to developing acne. About 81% of the variance in acne can be attributed to genetic factors, whilst 19% of variance in acne can be attributed to environmental factors;
• Excess androgen production, as can occur in some obese individuals, individuals with adrenal hyperplasia and other endocrine disorders: Structural modifications of the androgen receptors, thought to be genetic in origin, may play a role in altered response to peripheral androgens. Allelic variants in the cytochrome P450 gene, which may lead to defects in keratinocyte differentiation, have been observed in patients with acne;
• Excessive combing or brushing of hair;
• Sweating or a humid environment;
• Comedogenic cosmetics, such as those containing the agent isopropyl myristate;
• Stress;
• Hormonal changes, as can occur during pregnancy or with the use of oral contraceptives;
• Certain medications, including steroids and phenytoin.

Contrary to common perceptions, there is as much scientific evidence pointing to dietary factors as arguments against the significance of nutritional intake on the exacerbation of acne (e.g., fatty foods and chocolate). Consumption of healthy foods will, however, promote general well-being.

Pathology

Acne is a chronic disease of the pilosebaceous follicle. The pathophysiology of acne can be divided into three steps:

1. Stimulation of the sebaceous glands, resulting in seborrhoea. This step usually begins at puberty.
2. Defects in the proliferation, adhesion and differentiation of keratinocytes lead to micro-comedone formation. Micro-comedones are the first elementary lesions of acne.
3. Formation of inflammatory lesions constitutes the third step. Unlike the first two steps which are universal in the pathogenesis of acne, the third step does not occur in all individuals. Propionibacterium acnes (P acnes), a gram positive anaerobe, plays a crucial role in the formation of inflammatory lesions.

Androgens, in particular, a metabolite of testosterone, stimulate the production of sebum. A number of enzyme systems are present in the sebaceous glands and they convert cholesterol or weak androgens to stronger androgens that are capable of activating these glands. In patients with acne, the activity of these enzymes is increased. The rate of proliferation of sebocytes, the cells that form the sebaceous glands, and the potency of the enzyme systems varies between different cutaneous regions. This is believed to explain the predominance of facial acne. In addition, specific receptors (such as the PPAR receptor system that act via retinoid receptors) and neuromediators (such as substance P) can alter sebum production by modifying the proliferation of sebocytes and secreting specific substances respectively.

Obstruction of the follicular canal occurs due to defects in proliferation, adhesion and differentiation of keratinocytes. The keratinocytes fail to separate from each other, hence obstructing the canal and resulting in the formation of a micro-comedone, which is invisible to the naked eye. As the sebum production continues, dilation of the follicles occurs forming the comedone, which is visible. Anomalies in androgen metabolism are thought to play a role in causing the defects in keratinocyte proliferation, adhesion and differentiation. Interleukin-1α, a cytokine released by the keratinocytes in response to local irritation, is believed to play a role in micro-comedone formation. The phenomenon of seborrhoea, which decreases the concentration of linoleic acid in sebum by dilution, has been shown to affect keratinocyte differentiation and may contribute to the formation of micro-comedone.

P acnes plays a crucial role in the inflammatory phase of acne. P acnes proliferates in the micro-comedone and contains lipases that split triglycerides into free fatty acids and glycerol. The free fatty acids and bacterial fragments from P acnes migrate across the wall of the comedone and initiate an inflammatory response. Polynuclear neutrophils are recruited into the perifollicular tissue, where they secrete enzymes, including matrix metalloproteinases. These enzymes rupture the follicular wall and the inflammation invades the deeper layers. Other inflammatory mediators, such as T lymphocytes, prostaglandins, leukotrienes, complement, macrophages and cytokines, also play a role in the inflammatory response.

Symptoms

Acne usually occurs on the face and shoulders, but may also occur on the arms, legs and back. The symptoms of acne, in increasing order of severity, include:

• Blackheads (open comedone);
• Whiteheads (closed comedone);
• Inflammatory papules and pustules;
• Cysts; and/or
• Scarring of the skin.

Diagnosis of acne is based on the appearance of the skin. Clinical tests are not performed, unless clinically warranted.

Clinical features

Acne is considered a polymorphic disease (that is, it presents in multiple forms) and two patterns of disease can usually be noted. In non-inflammatory acne, often seen in the peri-pubertal age group (8-16), increased sebum production in the face, chest, back and shoulders results in the formation of blackheads or open comedones. In some instances, appearance of whiteheads or closed comedones can occur, heralding the progression to inflammatory disease.

The inflammatory disease associated with acne is characterised by the presence of blackheads, whiteheads, papules and pustules. Cystic nodules and scarring can also be present. Redness and seborrhoea (greasy skin due to excess secretion of sebum) can also occur. The presence of acne may persist over years. Nodules may become more painful and an increased risk of scarring is present. Following the inflammatory phase, red or hyperpigmented changes can occur, which can last several months or even few years. On the upper chest and shoulders, hypertrophic or keloid scarring (a type of fibrous scar) may develop. Atrophic or “ice-pick” scars may usually develop on the face. In addition, small depressions and slight discolouration can develop and last for up to 12 months.

Clinical features of acne conglobata

In acne conglobata, a rare, severe variant of acne vulgaris, nodules are interconnected by channels, which contain haemorrhage and purulent exudate. When this evolves rapidly with fever, arthritis and neutrophil leukocytosis, the condition is termed acne fulminans.

Diagnosis

Diagnosis of acne vulgaris is made clinically, based on the appearance of skin. Laboratory testing is rarely resorted to. Other conditions such as pustular drug eruptions and bacterial and fungal folliculitis can resemble acne, but can be distinguished by the absence of comedones. Acne rosacea can also resemble acne vulgaris, but the former is notable for its lack of comedones and nodules.

Although rarely performed, histological cultures may be helpful in ruling out gram-negative folliculitis (inflammation of the hair follicle) that is unresponsive to treatment. Histologically, a comedone is observed as a dilated follicle with a “plug” of loosely arranged keratin. As the disease progresses, dilation of the follicular opening occurs, resulting in an open comedone (blackhead). As the follicular wall thins, it may rupture. Bacteria and inflammatory mediators may be present. If the inflammation extends into the dermis, fibrosis and scarring can occur.

Treatments

Self treatment

The following self-care steps may aid in decreasing the severity of acne:

• Washing the skin with a mild, non-drying soap once or twice a day;
• Avoiding excessive washing of the skin;
• Avoiding comedogenic cosmetics, such as those containing the agent isopropyl myristate; and
• Avoiding rubbing, squeezing, scrubbing or picking the pimples.

Acrylate glue based products, sold at pharmacies, may be used at home to extract comedones. It should be noted that this is not the same as picking at the spots, which can lead to scarring.

Professional treatments

Physicians (or beauty therapists) may choose to extract comedones manually. Pursuing this treatment once or twice a month may, in combination with other treatment options, may lead to a quicker resolution of acne.
Prescription medicines include:

• Topical retinoid creams;
• Topical and oral antibiotic therapy;
• Benzoyl peroxide;
• Hormonal therapies.

For severe cases of acne, chemical skin peeling, removal of scars and cysts or photodynamic therapy (see below) may be warranted.

Early stage acne treatment: Keratolytic agents

Keratolytic agents are the most effective topical treatment for early-stage acne. These agents target the occlusion of the follicles. Keratolytic agents include:

• Retinoids: Tretinoin is considered as the gold standard against which new products are compared. It is the most potent of all the keratolytic agents. It acts by normalizing follicular epithelial cell turnover and preventing comedone formation. Side-effects include skin irritation, photosensitivity and an initial flare-up of acne. Adapalene, a synthetic napthoic acid derivative has comedolytic and anti-inflammatory properties and causes less irritation.
• Azelaic acid: is a naturally occurring dicarboxylic acid that normalizes hyperkeratinisation and has anti-inflammatory effects. It has anti-bacterial properties and can stop the growth of P acnes. Itching and burning sensations are occasional adverse effects.
• Alpha- and Beta-hydroxy acids: Both agents are comedolytics with limited efficacy.

Inflammatory phase acne treatment

For treatment of the inflammatory phase of acne that invariably involves P acnes, the following anti-inflammatory and antibiotic treatments are commonly prescribed:

• Benzoyl peroxide: a bactericidal drug that is available as an over-the-counter preparation. It reduces the number of comedones and acts by sterilizing the follicle via its antibacterial effects on P acnes. Dry skin and allergy are possible side-effects.
• Topical antibiotics: Clindamycin and erythromycin reduce numbers of P acnes. They also have anti-inflammatory actions by inhibiting neutrophil chemotaxis. A mixture of one of these agents with benzoyl peroxide may be more effective than either on its own and may aid in reducing antibiotic resistant strains of P acnes.
• Oral antibiotics: These agents are used in patients with moderate to severe forms of acne who are at risk of scarring. Tetracyclines, erythromycin and trimethoprim are the agents of choice. Adverse effects, such as hepatic and renal impairment, may occur, especially with long-term use, and biochemical monitoring may be helpful.

Anti-androgenic therapy, including combination oral contraceptives, may prove useful in the treatment of acne. It should be noted, however, that in some instances, the use of oral contraceptives may worsen acne.

Administering isotretinoin orally is helpful in treating nodulo-cystic acne. It suppresses the production of sebum to pre-pubertal levels and an associated decrease in P acnes is observed. Common adverse effects include skin dryness, dry cracked lips, retinoid dermatitis and dry mucous membranes. These side-effects usually resolve after ceasing therapy. In rare cases, acute fulminans can occur with isotretinoin therapy. Psychological impairment, such as depression and suicidal tendencies, can occur. Concomitant use with certain drugs should be avoided. Isotretinoin is contraindicated during pregnancy because of its teratogenic effects.

Photodynamic therapy for acne

Light and laser therapy may be used in combination with other therapies for acne in patients who do not respond to a single treatment option alone, or who experience significant adverse effects with other modes of treatment. The use of blue and other longer wave visible light stimulates production of natural porphyrins in P acnes and destroy target cells. Lasers and radiofrequency devices that are capable of general upper dermal cooling and causing selective injury to sebaceous glands can be helpful in the treatment of acne.

Prevention

Acne cannot be prevented. The following self-care steps may, however, aid in decreasing the severity of acne:

• Washing the skin with a mild, non-drying soap once or twice a day, especially after exercise;
• Avoiding excessive washing of the skin;
• Avoiding comedogenic cosmetics; and
• Avoiding rubbing, squeezing, scrubbing or picking the pimples.

No proven association exists between diet and acne, although consuming a healthy diet will promote general well-being.

Acne resolution

Acne usually resolves after adolescence. It may, however, recur or appear for the first time in adulthood in some individuals. Untreated acne can lead to the formation of painful cysts, and physical and emotional scarring. Consulting a general practitioner or dermatologist may be warranted, if the acne is severe or if it has not responded to over-the-counter treatments.

Although acne responds well to treatment, it may recur from time to time. The earlier the onset of acne, particularly in females, the more likely it is to recur in adulthood. It is important to note that like all medicines, treatment of acne may cause side effects – especially with tretinoin. Moreover, many of the commonly prescribed agents for acne are teratogenic and should be avoided during pregnancy.

References

• emedicine.com (2008) Acne vulgaris. [Online]. Available online [Accessed 01/12/2008].
• Goodman, G (2006). ‘Acne: natural history, facts and myths’. Australian Family Physician, Vol 35(8), pp. 613-616.
• Goodman, G (2006). ‘Managing acne vulgaris effectively’. Australian Family Physician, Vol 35(9), pp. 705-708.
• nlm.nih.gov (2008) Acne. [Online]. Available online [Accessed 01/12/2008].
• Pawin, H, Beylot, T, Chivot, M, Faure, M, Poli, F, Revuz, J & Dreno, B (2004). ‘Physiopathology of acne vulgaris: recent data, new understanding of the treatments’. European Journal of Dermatology, Vol 14, pp. 4-12.
• Purdy, S & de Berker, D (2006). ‘Acne’. British Medical Journal, Vol 333, pp. 949-953.
• Taglietti, M, Hawkins, C N & Rao, J (2008). ‘Novel Topical Drug Delivery Systems and Their Potential Use in Acne Vulgaris’. Skin Therapy Letter, Vol 13(5), pp. 6-8.
• Webster, G F (2002). ‘Acne vulgaris’. British Medical Journal, Vol 325, pp. 475-479.
• Zaenglein, A L & Thiboutot, D M (2006). ‘Expert Committee Recommendations for Acne Management’. Pediatrics, Vol 118, pp. 1188-1199.