Topical timolol reduced steroid-induced skin telangiectasia (visible blood vessels) by downregulating the antimicrobial peptide LL-37 through the KLK5 pathway.
Significant improvement by week 4Both rabbit and human subjects showed marked reduction in telangiectasia after 4 weeks of topical timolol, with the treatment working by downregulating the LL-37 antimicrobial peptide pathway.
What the researchers found
In the rabbit model, erythema, papules, and telangiectasia were significantly diminished after 4 weeks of timolol treatment. The antimicrobial peptide LL-37 and the enzyme KLK5 were elevated in steroid-damaged skin but decreased after timolol treatment.
In human patients with facial telangiectasia, cheeks treated with timolol plus tacrolimus showed markedly reduced telangiectasia compared to tacrolimus alone by week 4. Both groups showed reduced erythema by week 1, but the timolol combination was significantly superior for visible blood vessels. Color measurements confirmed significant differences in L (lightness) and a (redness) values between treatment and control cheeks (p<0.05).
Why it matters
Facial corticosteroid addiction dermatitis is a growing problem, particularly in regions where potent steroid creams are used long-term or inappropriately. The visible blood vessels are disfiguring and difficult to treat. This study identifies a new mechanistic pathway — abnormal LL-37 expression — and offers a simple, accessible treatment option using timolol, an inexpensive and widely available medication. The split-face design in humans provides particularly compelling evidence since each patient serves as their own control.
How the study worked
The study had two parts. First, rabbit ears were treated with flumethasone ointment to induce telangiectasia, then treated with 0.5% timolol eye drops twice daily for 4 weeks. LL-37 and KLK5 expression was measured by PCR. Second, human patients with facial telangiectasia served as their own controls — one cheek received timolol plus tacrolimus ointment, the other received tacrolimus alone for 8 weeks. Changes were tracked by dermoscopy and chromameter color measurements at weeks 1, 2, 4, and 8.
What this study cannot tell us
The human portion of the study did not specify the number of patients enrolled. The split-face design, while controlling for individual variation, only compared timolol+tacrolimus versus tacrolimus alone — there was no timolol-only or placebo arm. The 8-week follow-up is relatively short for a chronic condition. The rabbit model may not perfectly replicate human steroid-induced skin changes. The mechanism linking KLK5 to LL-37 in this context needs further investigation.
How to read the evidence
This study combines preclinical animal data with a split-face clinical trial in humans, providing mechanistic evidence alongside clinical observation. The split-face design is a strength, but the lack of reported patient numbers, short follow-up, and absence of a timolol-only arm limit the overall evidence quality.
When this study was published
Published in 2018, this study was among the early investigations of timolol for steroid-induced telangiectasia. The LL-37 mechanism it identified has since been explored further in dermatological research.
The bigger picture
LL-37, the only human cathelicidin, is increasingly recognized as more than just an antimicrobial peptide. It promotes angiogenesis (blood vessel formation), modulates inflammation, and plays roles in wound healing. Its abnormal expression has been implicated in rosacea, psoriasis, and now steroid-induced telangiectasia. This study adds to our understanding of how antimicrobial peptides can contribute to skin pathology when dysregulated, expanding potential therapeutic targets beyond infection control.
Questions still open
- Would timolol alone (without tacrolimus) be effective for steroid-induced telangiectasia, or is the combination necessary?
- What is the optimal duration and frequency of timolol treatment for long-term management of facial corticosteroid addiction dermatitis?
- Could LL-37 levels serve as a biomarker for predicting which patients will develop telangiectasia from steroid cream use?
Common questions
How does the antimicrobial peptide LL-37 cause visible blood vessels in steroid-damaged skin?
Can I use timolol eye drops on my face for steroid-damaged skin?
Read the original research
Inhibitory effect of timolol on topical glucocorticoid‑induced skin telangiectasia.
Molecular medicine reports, 18(3), 2823-2831
Citation
Li, Yan-Fei; Chen, Xiao-Yan; Lei, Tie-Chi. (2018). Inhibitory effect of timolol on topical glucocorticoid‑induced skin telangiectasia.. Molecular medicine reports, 18(3), 2823-2831. https://doi.org/10.3892/mmr.2018.9266