CIPLADOC - Current Medical Scene

Current Medical Scene
vol.17 No.3 July - September, 2002

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It is every collegian’s nightmare. But there is more to acne than being just a teenage problem. Acne vulgaris or acne is a very common skin disease affecting nearly 80% of people between the ages of 11 and 30. It can persist for years and result in disfigurement and permanent scarring. It can have serious adverse effects on psychosocial development, resulting in emotional problems, withdrawal from society and depression.
Acne vulgaris is a multifactorial disease affecting the pilo-sebaceous follicles. These follicles are the largest and most numerous on the face, upper back, and chest.
Pathophysiology
Acne begins in the prepubertal
period, when increased amounts
of adrenal androgens cause enlargement of the sebaceous glands. The glands step up the production of sebum. In the affected follicles, there is increased desquamation of follicular keratinocytes. The resulting follicular obstruction by the combination of sebum and desquamated epithelial cells causes the formation of a microcomedone, the precursor lesion of acne.
Meanwhile, the environment is ideal for a resident anaerobic organism, Propionibacterium acnes, to thrive. It produces chemotactic factors and proinflammatory mediators that may lead to inflammation. Outwardly, all these pathophysiologic events manifest as non-inflammatory comedones that may be open (blackheads) or closed (whiteheads). There may also be inflammatory papules, pustules nodules and cysts.
The disease can be graded on clinical grounds as under:

Grade I (Mild)	Comedones, occasional papules.
Grade II (Moderate)	Comedones, papules, a few pustules
Grade III (Severe)	Predominant pustules, nodules, and abscesses
Grade IV (Cystic)	Mainly cysts and abscesses, widespread scarring as inflammatory lesions resolve

Treatment Goals
Although acne is not a life-threatening disease, it has significant physical and psychological ramifications – permanent scarring, poor self-image, social inhibition, depression and anxiety. There are four main steps in the pathogenesis of acne:
• Excess production of sebum.
• Abnormal desquamation of epithelial cells in sebaceous follicles.
• Proliferation of P.acnes.
• Release of inflammatory mediators into the follicle and surrounding dermis.
These lead to formation of microcomedones and finally to the inflammatory lesions. Therefore, therapy for acne should aim at:
• Reduction of sebum production
• Reduction of epithelial desquamation in sebaceous follicles
• Prevention of proliferation of P.acnes
• Reduction of inflammation

Therapies for acne
Therapies for acne can be divided into two broad categories: Topical and systemic therapy.

TOPICAL AGENTS
Topical agents are the mainstay of treatment for mild to moderate acne. For mild to moderate (Grade I and II) non-inflammatory comedonal acne, the main thrust of therapy is preventive — minimise formation of new comedones and deny P. acnes a favourable environment to thrive. Hence, the most effective medications are the comedolytics and keratolytic agents. This group includes benzoyl peroxide, azelaic acid and the retinoids (tretinoin, adapalene).

Benzoyl peroxide: Topical benzoyl peroxide is a bacteriostatic and comedolytic agent useful for the treatment of mild to moderate acne. Its main side effects are excessive drying, irritation and allergic contact dermatitis.

Azelaic acid: It is antibacterial, it normalises keratinisation, and it is anti-inflammatory. Topical azelaic acid has some comedolytic activity. The most common adverse effects of azelaic acid are mild transient erythema and cutaneous irritation.

Retinoids: Topical tretinoin or adapalene is the treatment of choice for comedonal acne. Tretinoin is a potent comedolytic agent, and restores disturbed keratinisation. Topical adapalene has clinical benefits similar to tretinoin and causes less local irritation.

Topical antibiotics
Topical antibiotics like erythromycin, clindamycin, and tetracycline are used in inflammatory acne. They inhibit the growth of P.acnes but are ineffective in comedonal acne.

SYSTEMIC THERAPY
Systemic therapy includes, systemic antibiotics and oral isotretinoin.

Systemic antibiotics
Indications for systemic antibiotics include:
• Moderately severe or severe grades of acne where topical treatment frequently fails
• Chest and back involvement, as acne in these areas is less responsive to topical therapy.
Tetracyclines, doxycycline, erythro-mycin and minocycline are the drugs most commonly used. In patients with severely inflamed lesions, a combination of a topical and a systemic antibiotic is the best approach.
Some patients may develop a more destructive type of inflammation associated with large, deep inflammatory nodules (nodulo-cystic acne), which do not respond to the conventional oral and topical therapy. These cases require treatment with oral isotretinoin.

ISOTRETINOIN
Isotretinoin is so far the only agent, which acts on all pathological factors involved in the pathogenesis of acne. It is indicated for the treatment of nodulo-cystic acne and severe forms of acne that do not respond to conventional therapies. Nearly 90% of severe acne patients treated with oral isotretinoin achieve almost complete remission of their disease after a course lasting 12 to 16 weeks. The recommended dosage range for isotretinoin is 0.5 to 2 mg/kg given in two divided doses daily for 15 to 20 weeks.
The greatest concern regarding oral isotretinoin is its teratogenicity. Women of childbearing age must go for a pregnancy test prior to starting therapy. They must use effective contraception until at least one month after cessation of therapy.

Conclusion
Acne vulgaris is a disease that has profound psychological effects. The development of new drugs has dramatically altered the approach to the treatment of acne. Oral isotretinoin is a particularly effective agent in severe and stubborn cases, though its use must be tempered with caution on account of its side effects.

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