Low dose isotretinoin to treat rosacea
Papulo-pustular rosacea can be a very frustrating and distressing disease. The persistent development of papules and pustules at the central face can cause significant depression and reduction in quality of life.
The standard treatment ladder for rosacea is
- Avoid rosacea triggers
- Topical anti-inflammatory agents such as Metrogel and Finacea
- Systemic antibiotics such as tetracyclines or erythromycin
A minority of patients will not respond to the above and this is when low dose isotretinoin (0.1mg per Kg) may need to be used. Isotretinoin is a retinoid drug which has a number of different effects including
- Normalisation of keratinocyte (skin cell) growth to prevent oil gland blockages
- Reduction in oil production
- Anti-inflammatory effects
Isotretinoin is licensed for treating severe acne. High doses are needed (0.5 to 1 mg per Kg). It is not licensed for treating rosacea and it is important to know that when taking it for rosacea it is a un-licensed use. Isotretinoin treatment has a number of predictable side effects. The most significant is that it is very teratogenic. This means that it is highly likely to cause significant malformations in an unborn baby. Reliable contraception and close monitoring in a pregnancy prevention programme is needed if a woman of fertile age is to take Isotretinoin. Isotretinoin does not enter semen in significant quantities . The amount of isotretinoin transferred from a male to his female partner during intercourse is thought to be too low to pose a risk to the developing fetus. Although the risk is extremely low contraception has been recommended in more recent studies where the female partner is already pregnant.
Other side effects include dry skin, dry lips, increased sensitivity to sunlight, aching muscles and tiredness. There have been some reports of an effect on mood although there is not convincing data to confirm a link between isotretinoin and mood problems. This issue was recently reviewed by the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Why does low dose Isotretinoin work for rosacea?
The exact mechanism of action of isotretinoin in rosacea is unclear. Possible explanations depend on how what you believe the causes of rosacea to be.
One fact regarding rosacea inflammation is that in rosacea there is an increased amount of a pro-inflammatory protein caused cathelicidin, first described by Yamasaki et al. This protein is released by skin cells to kill unwanted bacteria. In rosaceal skin there is an excess of cathelicidin leading to redness and spots. The increase is due to an over activation of an enzyme called serine protease. This enzyme can be blocked by isotretinoin leading to a reduction in inflammation. Another theory relates to the demodex mites. A reduction in oil production may make the oil glands less appealing to the mites with a subsequent reduction in the number of mites leading to less inflammation.
These benefits only persist whilst the patient is taking isotretinoin and the rosacea will often return when the isotretinoin is stopped. This may also explain why a low dose can be used to treat rosacea; the enzymes that promote inflammation such a serine proteases can be inhibited by low dose isotretinoin whereas higher doses (used to treat acne) are needed to change the way that skin cells grow around and block oil ducts.
A number of clinical studies have demonstrated the effectiveness of low dose isotretinoin in the treatment of papulopustular rosacea including Erdogan et al and Gollnick et al.
The prescribing of low dose isotretinoin for rosacea is un-licensed in the UK. Many drugs are prescribed for diseases where they do not have a specific license. This is fine but full consent and careful monitoring is needed under the supervision of a Consultant Dermatologist.