What is oral isotretinoin?

Originally, the clinical indications for oral isotretinoin were selective and it was to be used only in patients with cystic acne which was severe and treatment-resistant. However, such reservations have changed over the years and now the indications for oral isotretinoin have expanded to include patients with recalcitrant acne, irrespective of its severity. Oral isotretinoin functions by opposing the contributory factors that lead to the development of acne. Oral isotretinoin also promotes skin cell differentiation and skin shedding. In so doing, it minimises the tendency for pores in the skin to clog and thus lessens the occurrence of acne.

The mechanism of action of oral isotretinoin:

In order to comprehend how oral isotretinoin works, it is important to first understand how acne develops. Although the causation of acne is multi-factorial, its development boils down to the process of inflammation within a pilosebaceous 1 unit in the skin. This is a consequence of increased sebum production which subsequently clogs the pilosebaceous unit with dirt, dead skin cells and Propionibacterium acnes (P.acnes) bacteria.

For one, oral isotretinoin makes sebaceous glands smaller and thus reduce the secretion of sebum. As such, a less favourable environment is created for the colonisation and proliferation of P.acnes bacteria, which subsequently minimises the inflammatory reaction that occurs in a pilosebaceous unit.

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Annoying Acne

Acne is an exasperating experience for all. While it is not physically debilitating, it does result in significant emotional distress for its victims. To make matters worse, some patients find themselves in a never-ending process of finding a cure to their acne; going from product to product, procedure to procedure but to no avail.
Although oral isotretinoin does promise to provide an end to the frustrating battle against acne, serious thought has to be put into the decision making process of whether or not to take a course of it. Apart from the very reason that oral isotretinoin may not be a solution for acne in the long term, one also has to bear in mind the consequences of taking this medication and be well prepared for it. More importantly, patients also have to recognise that the treatment of acne comprises of maintenance therapy as well. Hence, even when visible improvements are observed, a proper skincare regimen should still be adhered to in order to prevent relapses.

How are patients actually responding to oral isotretinoin?

In general, patients on oral isotretinoin can expect to see a substantial improvement of their acne and for some, even be acne free in four to six months after the initiation of their treatment. Although oral isotretinoin produces significant results in a considerably short period of time, recent clinical research has shed light that this drug is not a long term cure for acne. Multiple case studies have been conducted and it revealed a large number of patients who relapsed after completing their course of oral isotretinoin. Such cases have the highest occurrence within the first three years of ceasing treatment and also in patients who predominantly had truncal acne or were given a low dose of the drug (120mg/kg).
A suggested explanation for this high relapse rate was the poor adherence with the recommendation of taking oral isotretinoin together with high fat or high calorie content food. This recommendation stems from the mechanism of the drug which has an increased systemic exposure when it is being taken with high fat or high calorie meals; that is, there is an increased absorption of the drug by the body. Some medical practitioners however, may feel disconcerted over recommending such an unhealthy diet to their patients and hence advise them to take the medication just with food instead. It could also very well be a case of patients dismissing the
clinician’s advice to be on a high fat and high caloric diet while taking oral isotretinoin. While research has evidenced a noteworthy decrease in the bioavailability of isotretinoin when it is taken without food, more research is still needed on the impact on the bioavailability of the drug if meals with lower quantities of fat and calories were ingested instead.
Another possible reason why literature reports that oral isotretinoin is not a long term cure for acne could be due
to an increase in usage of this drug by younger patients. Younger patients have greater fluctuations in their
hormones as compared to a patient who is no longer an adolescent. Due to this very fact, younger patients have
a higher tendency to relapse after treatment and could possibly contribute to the higher numbers of relapse cases
in recent research.
Finally, the lack of maintenance therapy after recovery from acne could be another cause for a high rate of
relapse in patients. Although oral isotretinoin does provide significant improvement in one’s acne, it should be
no reason for one to be complacent after the treatment to follow-up with a proper skincare routine, topical
retinoids or even for some women, androgen treatment. Such measures have proven to prevent a relapse after
completing a course of isotretinoin.

Are there any side-effects for the miracle cure?

The most damaging side effect of oral isotretinoin would be its teratogenicity. Not only does it result in spontaneous abortions, oral isotretinoin is a cause of grave, and potentially lethal congenital malformations as well. Such adverse effects however apply only to women and are not caused by the usage of oral isotretinoin in men. It is thus pertinent for clinicians to adequately educate the users of this drug – particularly women of childbearing potential – to not be sexually active throughout the course of this medication. In the European Union for example, pregnancy testing is mandatory pre and post five weeks of treatment and is also made necessary for medical practitioners to reassess the patient’s pregnancy status once every four follow-up visits.
Apart from teratogenicity, oral isotretinoin also causes a notable increase in the levels of lipids, cholesterol and liver enzymes. As such, blood tests measuring the level of fasting serum lipids and cholesterol as well as liver function tests should be procured before treatment is initiated. Additionally, periodic tests for these three components should also be conducted and closely monitored. In the case that there is a marked abnormal result obtained from either one component, therapy needs to be stopped.
Oral isotretinoin results in dry skin and an increase in photosensitivity in its users too. Hence, it is prudent to counsel patients on these side effects and prepare them to expect chapped lips, possibly peeling dry skin, nose bleeds and also an increased tendency to get sunburnt. In light of this, patients should then be properly equipped with emollients and sunscreen in order to counteract these adverse effects. Additionally, procedures such as dermabrasion, chemical peels, laser treatments and waxing should be avoided as well in view of the fragility of the skin.
Finally, oral isotretinoin has reportedly made it to the top ten drugs under the Food and Drug Association to cause depression and suicide in its users. This link is still undergoing much research but some researchers have suggested that depression and suicidal ideation is attributed more to the emotional and psychological distress over the acne rather than oral isotretinoin itself. Nonetheless, it is still crucial for clinicians to closely follow-up with their patients and pick up any signs of depression or suicidal intent.