Rosacea is a common and troublesome facial dermatosis. The disease may occur in patients with any skin type, but in patients of Celtic and Scandinavian ancestry prevalence rates of up to 10% have been reported. Despite some progress in understanding the aetiology, treatment remains a challenge, with many patients achieving only partial control.
In this issue of the BJD, Webster et al. report the beneficial effects of topical minocycline on papulopustular rosacea. The precise mechanism of action of tetracyclines in rosacea remains unclear. Multiple anti-inflammatory effects have been reported including inhibition of proinflammatory cytokines and matrix metalloproteinases, scavenging of reactive oxygen species, inhibition of neutrophil migration and adherence and reduced proliferation of lymphocytes.
Innate skin immune system dysfunction appears to be the central problem in rosacea. Cathelicidin antimicrobial peptide (CAMP) is significantly overexpressed in rosaceal skin. CAMP gene expression is predominantly vitamin D dependent. This has prompted the theory that low winter vitamin D in northern Europe could have pushed the evolution of additional non-vitamin D-dependent innate immune pathways leading to lower thresholds for cutaneous inflammation in people with pale northern European skin types. Excess Demodex mites in rosaceal skin have been observed for 50 years, but a definite role in rosacea pathogenesis has only been accepted relatively recently, with publication of clear evidence of altered Toll-like receptor responses to Demodex mites. Chronic inflammation leads to lower thresholds for innate immune activation. Exaggerated responses to normal erythemal triggers such as heat, alcohol, wind and ultraviolet radiation usually occur first, followed by papulopustular eruptions, telangiectasia and, in selected patients, sebaceous hyperplasia, lymphoedema and sensory nerve dysfunction. There are clearly multiple molecular pathways affected in rosacea and it is therefore no surprise that tetracyclines, with their broad array of anti-inflammatory mechanisms, are so effective.
The choice of anti-inflammatory medication is not straightforward, with a variety of topical and systemic agents available. One of the most commonly used oral antibiotics, doxycycline, can also be useful for serious infections such as methicillin-resistant Staphylococcus aureus pneumonia, and antibiotic stewardship campaigns are trying to reduce unnecessary prescribing of oral antibiotics. Low-dose isotretinoin can be an effective alternative but it is unlicensed for rosacea and clearly comes with certain issues. Therefore, the investigation of topical minocycline published in this issue of the BJD by Webster et al. is welcome. Oral minocycline is no longer widely prescribed due to the significant adverse side-effect profile associated with systemic use.
Webster et al. report a multicentre, randomized, double-masked, parallel-group, vehicle-controlled study to evaluate the safety and efficacy of minocycline gel 1% and 3%. Topical minocycline had insignificant systemic absorption but produced significant reductions in mean inflammatory lesion counts with both the 1% and 3% concentrations. The response rate in the vehicle group was quite high, as is often the case in diseases with fluctuating inflammation. However, the 3% concentration of minocycline showed a significantly greater proportion of patients achieving Investigator's Global Assessment success at week 12 compared with vehicle. A topical minocycline foam formulation is in development, and this may provide a further useful option for treating papulopustular rosacea. How topical minocycline compares with other topical rosacea treatments is as yet unclear.
I am grateful to Dr Simon Meggitt for constructive comments during the development of this article.
The British Journal of Dermatology. 2020;183(3):412-413. © 2020 Blackwell Publishing