I've heard and read from multiple sources that acne gets worse during the first two weeks of treatment with isotretinoin, but I haven't been able to find an explanation as to why this happens.
From the American Academy of Family Physicians:
Your acne may get worse when you start using isotretinoin. This usually just lasts for a little while.
Isotretinoin works by reducing the production of the skin's natural oil (sebum) - Netdoctor UK. The half life of isotretinoin is 10-22 hours (Mortazavis et al., 2014), so it would take about a 5 days to week for the drug to reach steady state. In the meantime as the sebum production reduces, the skin dryness will stimulate the sebum glands to increase production causing a period of short term deterioration due to sebum over-production, before sebum production drops by two to four weeks. Another factor could be is that isotretinoin causes an increase in increase in epidermal cell turnover (Tadini, Gaspar & Campos, 2006). This can lead to sloughing, peeling, and redness that might make acne appear to be worsening when in fact it is a different skin process altogether.
There is also a more serious complication of starting isotretinoin which is a flare of acne fulminans. Acne fulminans is a severe form of inflammatory acne which usually require steroids resolve. Younger age, male sex and sebaceous retention are significant risk factors for acne fulminans, more specificially if the acne was severe to start with, there is more than 44 facial comedones, 2 facial nodules and presence of truncal acne (Demircay, Kus & Sur, 2008). However, now as isotretinoin is started at a lower dose and usually antibiotics and/or steroids are given for those at high risk making acne fulminans a far less common complication.
*References:
Demircay, Z., Sadiye, K., Haydar, S. (2008). Predictive factors for acne flare during isotretinoin treatment. European Journal of Dermatology. pg 452-6.
Mortazavi, H., Aghazadeh, N., Ghiasi, M., & Lajevardi, V. (2014). A review of three systemic retinoids in dermatology: Acitretin , isotretinoin and bexarotene. Iranian Journal of Dermatology.
Tadini, A., Gaspar, K., & Campos, P. (2006). Epidermal effects of tretinoin and isotretinoin: Influence of isomerism. Die Pharmazie, 61, 453–456.
This is a concept not unique to Isotretinoin, which is that of either:
Drug sensitivity happens as the body reacts to an initial exposure to a drug, before it builds a tolerance to it.
A drug allergy is different from an intolerance. A drug intolerance, which is often a milder, non-immune-mediated reaction, does not depend on prior exposure. [WP:Drug Allergy]
