Highlight
This real-world longitudinal study demonstrated that participation in a digital standardized skin care regimen (SSCG) alongside systemic doxycycline and topical azelaic acid significantly improved clinical clearance and reduced relapse rates in patients suffering from co-occurring acne and rosacea. Importantly, the study elucidated that improvements in inflammatory grading predicted reductions in transepidermal water loss (TEWL), partially mediating clinical benefit, while increased frequency of patient-provider communication did not show a dose-dependent effect on outcomes.
Study Background
Acne and rosacea are prevalent chronic inflammatory skin disorders with overlapping clinical features and frequent comorbidity, which complicates management. Rosacea commonly presents in adults, often with persistent erythema and inflammatory papules, while acne predominantly affects adolescents and young adults, characterized by follicular hyperkeratinization, sebum overproduction, and inflammatory lesions. Comorbidity of these conditions presents diagnostic and therapeutic challenges, as inflammation and barrier dysfunction mechanisms intertwine, and treatment responses vary.
Standardized skin care regimens have been proposed to optimize barrier function and reduce disease activity, yet evidence in comorbid acne-rosacea populations remains limited. Digital health platforms enabling regimen standardization and monitoring may enhance adherence and outcomes, but temporal and mechanistic understanding of their benefit is lacking. Furthermore, transepidermal water loss (TEWL), a noninvasive measure of skin barrier integrity, has been implicated mechanistically but its mediating role in clinical improvement is unclear.
Study Design
This investigation was a single-center retrospective longitudinal cohort study involving patients with confirmed dual diagnosis of acne and rosacea. All patients received an identical baseline pharmacologic treatment comprising systemic doxycycline and topical azelaic acid. Participants were divided into those who engaged with a digital standardized skin care regimen (SSCG) and a matched cohort who did not, using propensity score matching to control confounding and achieve 282 pairs.
The primary clinical endpoint was the Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear) at 12 weeks. Secondary outcomes included relapse rates, quality of life improvement measured by dermatology life quality index (DLQI) minimal clinically important difference (MCID) attainment, and skin barrier integrity via TEWL measurements. Analytical methods featured cross-lagged panel models to investigate temporal relationships between clinical severity and TEWL, mediation analysis to quantify TEWL’s role in clinical outcomes, and E-value methodology to assess potential unmeasured confounding. Communication frequency with healthcare providers was examined regarding dose-response effects.
Key Findings
At week 12, SSCG participants achieved significantly higher rates of clinical clearance (IGA 0/1) compared to the non-SSCG cohort (54.6% vs. 34.4%), yielding a relative risk (RR) of 1.59 (95% CI 1.31–1.92). Relapse rates were notably reduced in the SSCG group (18.8% vs. 34.0%). Quality of life improvements were more pronounced, with 91.1% of SSCG participants reaching DLQI MCID versus 71.3% in controls.
Temporal analysis using a cross-lagged model revealed that improved IGA scores at week 6 significantly predicted subsequent reductions in TEWL at week 12, suggesting that clinical improvement in inflammatory status precedes and possibly facilitates barrier repair. The reciprocal path from TEWL to IGA was not statistically significant, indicating that changes in skin barrier, while important, are downstream of clinical inflammatory changes.
Mediation analysis estimated that TEWL reduction mediated approximately 12.4% of the SSCG-associated clinical benefit, highlighting a partial but important mechanistic pathway. Communication frequency analysis found no evidence for a dose-response relationship regarding outcome improvements, suggesting that regimen participation and adherence rather than communication alone drive benefit.
Safety data and adverse events were not explicitly detailed, aligning with real-world study limitations and the known safety profiles of doxycycline and azelaic acid. The digital SSCG intervention bundled skin care recommendations and education delivery but could not isolate individual component effects.
Expert Commentary
This study contributes important real-world evidence to support structured digital skin care interventions as adjunctive tools in managing the complex comorbidity of acne and rosacea. The use of robust statistical modeling to determine causality directionality and mediation by TEWL advances mechanistic understanding and underscores the integral role of epidermal barrier restoration in clinical improvement.
However, readers should interpret findings within context of limitations: the retrospective design allows associations but not definite causality; potential self-selection bias in SSCG engagement and cost-related factors may confound results; adherence was assessed by chart review rather than direct measurement; and unmeasured variables such as environmental exposures and contraceptive changes were not controlled.
Clinicians should recognize that combining pharmacotherapy with a standardized digital regimen may augment outcomes by promoting consistent skin care and supporting barrier repair—key factors in disease control. Future prospective, randomized studies are needed to dissect specific regimen components, confirm mediation mechanisms, and evaluate long-term sustainability and safety.
Conclusion
In this well-characterized cohort of patients with acne-rosacea comorbidity, participation in a digital standardized skin care regimen alongside doxycycline and azelaic acid was associated with enhanced clinical clearance, reduced relapse, and improved quality of life. The partial mediation by transepidermal water loss reduction supports the concept that restoration of epidermal barrier function contributes to treatment efficacy. These associative and hypothesis-generating findings advocate for integrating digital health solutions into dermatologic care pathways for complex inflammatory skin diseases, though randomized controlled trials remain warranted to confirm benefit and delineate mechanisms.
Funding and Clinical Trials Registration
The publication does not report funding sources or clinical trial registration details, reflecting its retrospective cohort nature.
References
- Tan JKL, et al. Rosacea: current state of epidemiology, pathogenesis, and treatment options. J Eur Acad Dermatol Venereol. 2021;35(1):25-36.
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- Steinhoff M, et al. Comorbidities and pathophysiology of rosacea and acne: a review. J Eur Acad Dermatol Venereol. 2022;36(2):205-217.
- Fowler JF Jr, et al. Efficacy of a topical azelaic acid solution in papulopustular rosacea. J Drugs Dermatol. 2007;6(1):53-6.
- Baumann LS. Acne and rosacea: role of barrier dysfunction. Dermatol Ther. 2022;35(1):e15230.
