Isotretinoin (13-cis-retinoic acid) has revolutionized the life of patients with severe acne. It has been shown to be far superior to placebo and better than conventional  therapy - erythromycin 1 g/day plus 5  per cent benzoyl peroxide, tetracycline and retinoic acid topically and etretinate.

  Initially isotretinoin was given only to subjects  with exceptionally severe acne but most dermatologists now use it in other situations: 1 The patient  whose  acne has done  reasonably  well with  conventional  therapy  but,   despite  several changes of therapy,  is not improving. The patient whose acne has responded well to conventional oral treatment on two or three occasions but has relapsed very quickly on stopping oral therapy. The patient with Gram-negative folliculitis.

The dysmorphobic patient. In a  multicentre study  forty patients  suffering from severe papulopustular acne previously resistant to therapy were treated with isotretinoin at a dosage of 0.05, 0.1 or 0.2 mg/kg body weight for twenty weeks.

After treatment,  they performed follow-up examinations for twelve months concerning remission and  side-effects. After six months more than half the patients were free of relapses, even those treated with low doses, although there was a trend in favour of the higher 0.2 mg/kg body weight dose.

  Side-effects are very frequent with isotretinoin and at times troublesome.  Isotretinoin is teratogenic and the female  patient must not become pregnant when taking the drug and for one month after the course of therapy is discontinued. The patient must also be told  to avoid vitamin A supplements  which would increase the risk of hypervitaminosis A. Neither should tetracycline  or tetracycline-like drugs be  taken as these increase the risk of intracranial hypertension.

  Additional topical acne therapy is not required with isotretinoin. However, a few months after stopping isotretinoin it  is usual for a few relatively insignificant lesions to return and the patient may, not unreasonably, wish then to use topical therapy.

 Isotretinoin dramatically  and  quickly  suppresses ebum excretion this oppression is maintained for many months in a doseependent manner. Previous chapters have indicated possible important role of linoleic acid in comedogenesis.  A low level may be of aetiological significance. Conversely the therapeutic effect of isotretinoin may, at least in part, result from a significant increase in the linoleate content of sebum during treatment, resulting from the sebosuppressive  effect of the drug. The drug also suppresses comedogenesis as measured by the follicular  cast method.

These changes are probably a primary event . Isotretinoin produces considerable ultrastructural changes in the ductal corneocytes (Table 16.11): in particular, loss of cell-to-cell adhesion, desmosomal damage  and the accumulation of an amyloidlike  material  between the cells. Dalziel et al found no evidence for isotretinoin affecting  follicular  keratinization  and  so  these  striking changes probably represent an effect  on cell  to  cell adhesion.

  Isotretinoin does not directly affect P. acnes but in vivo it suppresses the  surface bacteria, in particular P. acnes,  by 3 log cycles  . This effect is due to a reduction in the nutrient supply of P. acnes and a reduction in the size of the follicular space where P. acnes grows. The antimicrobial effect, at least as far as the surface organisms are concerned, is  lost within a few months of stopping the drug on doses of less  than  1 mg kg day. However, on  doses  of  and greater than 1 mg/kg/day a suppression in the P. acnes counts is maintained for at least five months.

  Isotretinoin also influences  acne inflammation. It reduces chemotaxis of  polymorphonucleocytes  and monocytes, and reduces  pustule formation at the site of a potassium iodide patch81 (a method used for investigating follicular inflammation). Isotretinoin  also has varied effects on T and B  lymphocytes and complement but whether  this is specific to isotretinoin or simply due to improvement in the acne needs to be investigated.