Rosacea — a chronic inflammatory skin condition with a global prevalence of up to 5.5% — remains one of the most challenging problems in dermatology and aesthetic medicine. Clinical features include persistent erythema, telangiectasias, and flushing; in the papulopustular (PPR) subtype, papules and pustules significantly impair patients' quality of life. PPR is the most prevalent form of the disease. It is frequently associated with pronounced skin barrier dysfunction [2]: elevated transepidermal water loss (TEWL), reduced stratum corneum hydration, and altered skin pH. These disturbances close a vicious cycle that sustains and amplifies inflammation. For this reason, restoring barrier function alongside controlling inflammation is recognized as a strategic priority in rosacea management.

Conventional treatment options — topical and systemic antibiotics, retinoids, beta-blockers — carry a risk of side effects, including allergic reactions, gastrointestinal discomfort, and hepatic burden. Laser therapy is effective but requires prolonged treatment courses and considerable expense. Among chemical peel agents, salicylic acid (SA) stands out as a particularly interesting candidate — but with a caveat.

Why conventional SA-based preparations are problematic

Salicylic acid is a beta-hydroxy acid (BHA) with high lipophilicity and well-documented keratolytic, anti-inflammatory, and antimicrobial properties. While its anti-inflammatory activity is desirable in PPR, the same keratolytic effect becomes a serious obstacle.

The skin in rosacea is already compromised: the barrier is weakened, and reactivity is heightened. Using standard SA-based peels in such patients carries a high risk of irritation, burning, redness, and exacerbation of inflammation. In practice, the agent theoretically best suited for controlling PPR proves unsuitable for the very patients who need it most.

The supramolecular form: how the molecule was changed

The answer lies in supramolecular salicylic acid (SSA) — a formulation in which SA is covalently bound to the water-soluble polymer poloxamer 407. This technology fundamentally alters the molecule's behavior both in the preparation and on the skin: SSA acquires a stable structure, dissolves in water, and releases the active ingredient slowly and steadily.

Sustained release enhances SA bioavailability while simultaneously reducing irritation potential — making SSA potentially suitable for sensitive skin with a compromised barrier. Previously, 30% SSA had been studied primarily in combination regimens — alongside minocycline [4] and metronidazole [3] — and its use in acne monotherapy had also shown promising results [5]. However, data on the standalone efficacy of 30% SSA in PPR remained clearly insufficient.

Study design

Researchers from the First Hospital of China Medical University (Shenyang) conducted a randomized, controlled, single-center study [1]. Between July and December 2020, 34 patients aged 18 to 60 years with PPR diagnosed according to the 2017 National Rosacea Society criteria were enrolled. Participants were randomly assigned to an experimental group receiving 30% SSA or a control group receiving a placebo (the vehicle matrix without the active ingredient). Procedures were performed once every two weeks for a total of four sessions.

At each visit, facial photography was performed using the VISIA skin analysis system. Efficacy was assessed by papule and pustule counts, Investigator Severity Assessment (ISA) scores (0–4 scale), the VISIA red area index, and skin barrier parameters: TEWL, sebum levels, stratum corneum hydration, and pH. Barrier parameters were measured in 17 of the 31 participants who completed the study (9 in the experimental group and 8 in the control group).

Three patients dropped out — one due to a suspected allergic reaction, and two who withdrew after the first visit.

Key results: the numbers speak for themselves

The data were compelling. Across the primary clinical endpoints, the 30% SSA group demonstrated:

• Treatment response rate (combined cases of significant improvement and complete resolution): 68.75% versus 0% in the placebo group (p<0.01).
• Total lesion count decreased from 38.06±10.40 to 13.19±7.30 (p<0.01); no significant change was observed in the control group (36.53±9.96 → 29.93±7.69, p>0.05).
• ISA score decreased from 2.94±0.68 to 1.75±0.68 (p<0.01), a statistically significant difference from the control group at the final visit.
• VISIA red area index improved by 25.1% in the experimental group and showed no change in the control group.

Skin barrier outcomes were equally encouraging:

• Sebum levels decreased significantly on both cheeks and the forehead (p<0.05), consistent with the expected lipolytic action of SA. No significant change was observed on the nose — the authors attribute this to the protocol requirement of applying petrolatum to the perinasal zone during the peel, which restricted SSA contact with that area.
• Stratum corneum hydration increased significantly on both cheeks and the nose (p<0.05). Unlike several earlier studies, the authors recorded not merely a trend toward improvement but a statistically significant increase, attributing this to the anti-inflammatory action of SSA, which normalizes keratinocyte function.
• TEWL and skin pH showed no significant changes: SSA appears to have a limited impact on these parameters.

The authors also highlight an important pattern: a noticeable reduction in lesion count was not observed until the third visit — that is, four to six weeks after treatment began. This is consistent with the nature of chemical peels: the initial session primarily removes superficial keratin without addressing deeper inflammatory lesions. Managing patient expectations during the early phase of treatment, the authors emphasize, is an essential condition for optimal outcomes.

Safety and adverse events

Tolerability of 30% SSA was good. All patients in the experimental group reported only a negligible burning sensation during the procedure; one patient described it as slightly more noticeable, though it remained tolerable and did not interrupt treatment. No signs of systemic toxicity were observed. In the control group, one patient discontinued following the first session after developing marked facial erythema, pruritus, and burning one hour post-procedure — a reaction suspected to be an allergy to components of the placebo or the cooling compress.

The authors recommend particular caution when prescribing SSA to patients taking aspirin or other salicylate-containing medications, and advise careful monitoring of the peel endpoint throughout the course of therapy to avoid over-exfoliation.

Limitations

The authors are transparent about the study's limitations. The sample size was small — 31 patients completed the study — which constrains statistical power. The design did not incorporate biopsies, serum inflammatory markers, or infrared confocal microscopy, which could have provided a more comprehensive picture of SSA's effect on inflammation. Finally, the post-treatment follow-up period was only two weeks, which is insufficient given rosacea's high recurrence rate. The authors state their intention to address these limitations in future studies.

Practical implications

These findings build an evidence base for 30% SSA as an independent topical agent in PPR management. For the practicing skincare specialist, the combination of effects is particularly noteworthy: the preparation simultaneously reduces the inflammatory lesion count, attenuates persistent erythema, lowers sebum levels, and improves stratum corneum hydration — addressing several pathogenetically relevant targets in a single course of treatment. The tolerability profile in patients with baseline skin barrier compromise was acceptable.

The authors do, however, point to the need to refine the application technique: the standard protocol requiring petrolatum application in sensitive areas and the use of rubber gloves reduced efficacy over the nose. Developing an optimized protocol for the use of SSA in rosacea remains a meaningful clinical challenge. The accumulated evidence from combination regimens [3, 4], together with the present findings, positions SSA as a flexible tool — both as a standalone option and as part of a comprehensive management strategy for PPR patients.

Conclusion

30% supramolecular salicylic acid demonstrated clinically meaningful efficacy in papulopustular rosacea in a randomized controlled trial: the treatment response rate was 68.75% versus 0% in the placebo group. The agent reduced papule and pustule counts, attenuated persistent erythema, and positively influenced skin barrier function — lowering sebum levels and increasing stratum corneum hydration. TEWL and skin pH showed no statistically significant changes. The safety profile was favorable, with adverse events limited to mild burning during the procedure. These findings broaden the evidence base for SSA in PPR and lay the groundwork for larger studies with extended follow-up.

References

1. Wang Z., Wu Y., Nozzari Varkani F. et al. 30% supramolecular salicylic acid improved symptoms and skin barrier in papulopustular rosacea. J Cosmet Dermatol 2025; 24: e70046.
2. Medgyesi B., Dajnoki Z., Béke G. et al. Rosacea is characterized by a profoundly diminished skin barrier. J Invest Dermatol. 2020; 140(10): 1938–1950.
3. Xu L., Yao B., Xu T., Huang H. Assessment of the efficacy and safety of 30% supramolecular salicylic acid peeling for papulopustular rosacea treatment. Indian J Dermatol 2022; 67(5): 625.
4. Wang L., Li X.H, Wen X. et al. Retrospective analysis of 19 papulopustular rosacea cases treated with oral minocycline and supramolecular salicylic acid 30% chemical peels. Exp Ther Med 2020; 20(2): 1048–1052.
5. Zhang L., Shao X., Chen Y.et al. 30% supramolecular salicylic acid peels effectively treats acne vulgaris and reduces facial sebum. J Cosmet Dermatol 2022; 21(8): 3398–3405.