Oral retinoid drugs in acne treatment

Oral isotretinoin, or 13-cis-retinoic acid, is currently the best oral retinoid and the best drug to combat severe acne. It has been in use for acne treatment for more than 20 years. It significantly reduces sebum secretion, comedone formation and propionibacterium or P. acnes on the skin and it also has anti-inflammatory properties.

Patients with severe acne that resists treatment with combined oral and topical therapy are the proper subjects for oral isotretinoin therapy. However, clinical experience has shown that oral isotretinoin can also be used with success in mild or moderate acne which is resistant to long-term oral or topical treatment. It can also be used in acne cases where there are severe scarring and psychological problems. Isotreinoin should never be used during pregnancy, lactation and in people with hepatic and renal disorders.

Before starting isotretinoin therapy, the severity of the disease should be well assessed. The assessment should include the likely effect of acne on the patient such as the potential for scarring. Isotretinoin acts in four ways. It reduces the size and secretions of the sebaceous glands, secondarily it inhibits the growth of P. acnes and the resulting inflammation, and prevents comedogenesis through normalization of the differentiation of the follicular keratinocytes. Isotretinoin thus affects all four pathogenic factors of acne and is the only drug that does so, revolutionizing the treatment of severe acne. This explains its nearly universal efficacy during active therapy. Moreover, it is the only treatment which can lead to permanent remission.

In isotretinoin therapy the dosage must be decided after considering the risk factor of the patient. Generally, 50% reduction of pustules is observed after 2 to 4 weeks of treatment. For the majority of patients, 6-month treatment duration is enough, but to get optimal results a low dosage treatment should be continued. Improvement continues during this post treatment period. Approximately 40% of patients remain free of acne after one course of treatment, 40% have a recurrence of low severity that responds to medications to which the acne had been previously been resistant and 20% will need repeated treatment with isotretinoin at a future time.

Relapses may occur after one six-month treatment course. Patients younger than 16 years, those with severe acne on the trunk and adult women are more likely than others to have a relapse. These first two groups may require multiple courses of isotretinoin over the duration of their acne prone years. Relapses, requiring repeated treatment, are higher among patients with severe acne who receive a low dosage treatment, compared to those receiving higher dosages of isotretinoin. The chance of a prolonged remission is greater when a total dose of 120mg to 150mg per kg of body weight is achieved. Most patients can be started on a dose of 20mg to 40mg per day with an increase to 40mg to 80mg over several months.

Side effects

Systemic isotretinoin therapy has numerous side effects. The two most important ones are related to isotretinoin teratogenecity and psychological effects.

Isotretinoin is a potent teratogen. In pregnancies affected by isotretinoin, 50% end up as spontaneous abortions and another 25% have neonatal cardiovascular or bone related abnormalities. Such abnormalities have been reported after a single dose. Women of childbearing age should be closely monitored for pregnancy prevention. They should test negative for pregnancy before starting treatment and the dermatologist should ensure that they are on effective contraception 1 month before the start, throughout and up to 6 weeks after discontinuation of isotretinoin treatment.

The psychological status of the patient should also be monitored carefully. Psychological disorders like depression, irritability and suicidal tendencies have been reported during and after isotretinoin therapy. Although studies have not confirmed any association between the use of isotretinoin and these psychological disorders, such events should be expected and the patient should have physicians and counselors at hand for immediate help. These disorders tend to disappear after stoppage of treatment, but recur with the resumption of treatment.

Mucocutaneous side effects are most common. These include dryness of the lips which affects all isotretinoin users, dry skin affecting 50%, nasal passages affecting 30% to 35% and dry eyes affecting 20%. To cure dryness moisturizers and lip balms are used.

The drug, however, has serious opthamalogic and gastro-intestinal side effect potential. Isotretinoin may cause hypertriglyceridemia and to a lesser extent affect cholesterol levels.

Side effects of therapy may be limited with reduced doses or by dietary changes over an extended period, allowing treatment to continue. However, reduction of dosage may cause relapse. Most side effects are tolerable and treatable.