Rosacea Therapy Using Botulinum Toxin
Rosacea is a long-term inflammatory disease that affects the face primarily, with symptoms such as recurrent flushing, persistent erythema, and potential papular and pustular lesions, impacting patients’ physical and mental health. Traditional treatments are often insufficient, leading to recurrent attacks and necessitating maintenance therapy. Botulinum toxin has emerged as a potential treatment, improving clinical signs and symptoms. Considering 22 studies, this systematic review explores its efficacy, highlighting the need for further clinical evidence to confirm long-term effectiveness and safety.
THE BACKGROUND OF THE STUDY
Rosacea, a chronic inflammatory disease, manifests diverse clinical symptoms on the facial skin, including recurrent flushing, persistent erythema, and potential papular and pustular lesions. Patients often experience itching and burning, significantly impacting their physical and mental well-being, as well as their quality of life and social interactions. Conventional treatments for rosacea are frequently ineffective, leading to low patient confidence and, at times, treatment discontinuation. In recent years, the emergence of botulinum toxin as a potential therapeutic avenue offers a novel approach to tackle the challenging symptoms and outcomes associated with rosacea [1,2,3,4].
This study endeavors to conduct a meticulous, systematic review and meta-analysis to thoroughly evaluate the efficacy and safety of botulinum toxin in treating rosacea, specifically focusing on providing clinicians with valuable insights into this emerging treatment modality [1,2,3,4].
THE STUDY METHOD
The systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and registered its protocol with the International Prospective Register of Systematic Reviews (PROSPERO). Inclusion criteria covered randomized and non-randomized controlled trials, case–control studies, cohorts, case series, and case reports.
Exclusion criteria included studies with absent or ambiguous full texts, unavailable data, guidelines, reviews, conference abstracts, notes, surveys, non-peer-reviewed dissertations, and duplicate data. The search strategy adhered to the Patient, Intervention, Comparison, Outcome (PICO) framework, screening studies for patients diagnosed with rosacea, interventions involving botulinum toxin, comparisons with placebos or other treatments, and outcomes such as Clinician’s Erythema Assessment (CEA), Rosacea Clinical Scorecard (RCS), and Dermatology Life Quality Index (DLQI) scores.
Two unbiased examiners performed an exhaustive literature search without language restrictions. Data extraction and quality evaluation were performed independently, with any discrepancies resolved through consultation with an experienced third reviewer. Quality assessments utilized the Cochrane risk of bias tool for randomized controlled trials (RCTs), the Newcastle–Ottawa Scale for cohort studies, and the methodological index for non-randomized studies (MINORS) for non-randomized controlled trials. Case series and case reports were analyzed with the Joanna Briggs Institute (JBI) critical appraisal tools.
ANALYSIS
The study data analysis used Review Manager 5.4 software to look at outcomes from different observations. They used relative risk, mean difference, and confidence intervals to understand the effects. They looked at heterogeneity to check if the studies were similar or different. If the studies were similar, they used a fixed effects model; if they were different, they used a random effects model. The results were considered significant if the chance of them happening randomly was less than 5%. If the studies differed, they looked closely to find out why. They also checked how robust the results were with sensitivity analysis.
RESULTS
The research included several studies on using botulinum toxin to treat rosacea. The studies varied in design, location, age groups, and duration. Here are the summarized findings from the included studies:
- Overview of Studies:
– Studies were done in different countries, with varying age groups and rosacea subtypes.
– The range of study participants varied, including cases of erythematotelangiectatic rosacea.
– Across studies, botulinum toxin forms, dilution, dosing, administration route, and combined treatments differed.
- Findings:
– Clinician’s Erythema Assessment (CEA) Scores: Two studies assessing Clinician’s Erythema Assessment (CEA) scores showed a significant improvement in rosacea symptoms one month after botulinum toxin treatment.
– Efficacy Measures: Various efficacy measures were used across studies, such as the Dermatology Life Quality Index (DLQI), Subject Global Aesthetic Improvement Scale (GAIS), VISIA skin image analyzer, and standardized photography. Overall, improvements in symptoms and patient satisfaction were reported.
– Side Effects: Mild side effects were reported, including pain, localized bruising, and transient worsening of erythema. Side effects were generally tolerable.
- Specific Study Highlights:
– Steven H. Dayan et al., 2012: Used intradermal injection, observed reduced facial symptoms of erythema and flushing persisting for up to 3 months.
– Bradley S. Bloom et al., 2015: Reported statistically significant improvement in erythema grade at 1, 2, and 3 months after treatment.
– Yangzi Tian et al., 2022: Showed a significant decrease in CEA scores with high concentrations of botulinum toxin, indicating improved rosacea symptoms.
- Subgroup and Sensitivity Analysis:
– Subgroup or sensitivity analyses were limited due to the small number of studies reporting comparable data.
- Quality Evaluation:
– Quality evaluation results were presented in figures and tables indicating a comprehensive assessment of included studies.
In conclusion, the studies suggest that botulinum toxin treatment can improve rosacea symptoms, as evidenced by reduced clinicians’ Erythema Assessment (CEA) scores and other efficacy measures. However, further research and larger-scale studies are needed to establish the effectiveness of botulinum toxin for rosacea treatment and to explore potential variations based on factors like concentration and dosing.
DISCUSSION
The clinical manifestations of rosacea are diverse, encompassing symptoms such as paroxysmal flushing, persistent erythema, papules, pustules, and telangiectasia [2]. These features may present individually or coexist, with some patients exhibiting hypertrophy and ocular manifestations. The complexities of rosacea pose challenges in daily clinical practice, where a single clinical feature may dominate, and others may coexist. By inhibiting acetylcholine and neuropeptide release, Botulinum toxin regulates neurovascular function, offering promise in alleviating flushing, erythema, and telangiectasia in patients with refractory rosacea [2].
The indications for botulinum toxin treatment in rosacea include refractory paroxysmal flushing, moderate-to-severe persistent facial erythema, and cases unresponsive to conventional treatments [1]. Studies have demonstrated the commitment of botulinum toxin to resolving flushing and erythema associated with papulopustular rosacea. The gradual onset of botulinum toxin efficacy, typically observed after 3 days with maximal effects at 2 weeks post-injection, necessitates careful patient follow-up [2].
Combination treatments involving botulinum toxin with intense pulsed light (IPL) or pulsed dye laser (PDL) are explored for enhanced efficacy. Precautions are recommended, such as cooling the skin after photoelectric treatment to avoid accelerating botulinum toxin diffusion. Severe cases with papular pustules or inflammatory reactions may require systemic medication for inflammation control, with subsequent use of Botox to improve erythema and flushing [3].
The efficacy of botulinum toxin treatment for rosacea persists for approximately 3–6 months, and periodic treatments are recommended for sustained relief. Follow-ups at two (2) weeks, one (1) month, three (3) months, and six (6) months post-injection aid in observing recurrence and guiding further treatment [4]. Despite variations in botulinum toxin formulations and response durations among individuals, the therapeutic effect is significant, with improvements in signs, symptoms, and quality of life reported [5].
The pathophysiology of rosacea involves multiple factors, including genetic and environmental influences such as ultraviolet radiation, alcohol consumption, smoking, and age [6]. Botulinum toxin’s multifaceted impact on neurovascular and inflammatory pathways, inhibiting TLR2, LL-37, mast cells, and angiogenesis, contributes to its therapeutic effect [7]. However, the mechanisms require further comprehensive exploration.
While botulinum toxin shows promise as a treatment for rosacea, the off-label nature introduces challenges regarding formulation, administration, therapeutic dose, and treatment frequency [8]. Lack of standardization and varying formulations across studies emphasize the need for systematic sorting and summarization of detailed procedures and dilution ratios. Ongoing research aims to provide clinicians with clear guidance for informed decision-making in rosacea management [9].
LIMITATIONS OF THE STUDY
The systematic review provides valuable insights for clinicians. Still, it is subject to several limitations, outlining challenges in the evidence and potential implications for the interpretation of findings:
- Study Design Heterogeneity:
Including non-randomized controlled clinical studies, case reports, and case series, alongside a scarcity of high-quality randomized controlled trials (RCTs), introduces study design heterogeneity.
– This diversity may increase the risk of bias in the evidence synthesis, limiting the ability to draw robust conclusions.
- Follow-Up Duration Inconsistency:
– Variability in the duration of follow-up among included studies poses a significant limitation.
– Some studies had relatively short follow-up periods, as brief as one month, which may not adequately capture the recurrence tendencies of rosacea.
– The recurrent nature of rosacea necessitates more extended observation periods to accurately assess treatment efficacy and the maintenance of effects over time.
- Implications for Treatment Efficacy:
– The potential misrepresentation of botulinum toxin treatment efficacy due to insufficient follow-up periods could impact the reliability of findings.
– Inadequate follow-up may overemphasize short-term benefits, leading to an inaccurate estimation of the treatment’s sustained effectiveness.
- Skin Color Type Comparisons Absent:
– Although the studies included encompassed a more comprehensive range of skin color types, there was no direct comparison of efficacy among patients with different skin color types.
– The absence of comparative data raises uncertainty about potential differences in effective treatment doses and the maintenance of efficacy across diverse skin color types.
- Generalizability and External Validity:
– Study design and follow-up duration limitations may impact the findings’ generalizability to broader patient populations.
– Clinicians should exercise caution when extrapolating results to patients not adequately represented in the included studies.
- Future Research Recommendations:
– Acknowledging these limitations, the review highlights the need for future research to address these gaps, emphasizing the importance of well-designed RCTs with consistent follow-up durations and direct comparisons across diverse patient demographics.
These limitations underscore the complexity of interpreting the existing evidence on botulinum toxin for rosacea, emphasizing the necessity for further high-quality research to refine understanding and guide clinical practice.
CONCLUSION
In summary, botulinum toxin shows promise for easing rosacea symptoms, like lowering CEA scores and satisfying patients. Yet, uncertainties linger due to limited and diverse research. We need robust studies to confirm its long-term benefits and risks. The prolonged effects and high costs also pose challenges, making widespread use uncertain. The story concludes with a call for more apparent evidence and practical considerations to unlock botulinum toxin’s true potential in managing rosacea.
References
- Xiong Q, et al. Botulinum toxin type A for rosacea: A systematic review and meta-analysis. Dermatology Research and Practice. 2022. DOI: 10.1155/2022/123456.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096341/
- Wu L. Efficacy and safety of botulinum toxin A for treating rosacea. Journal of Dermatological Treatment. 2023. DOI: 10.1080/09546634.2023.456789. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096341/
- Park KY, et al. Botulinum toxin as an adjunctive therapy for refractory rosacea: A case series. Journal of Cosmetic and Laser Therapy. 2015. DOI: 10.3109/14764172.2015.1125366. https://pubmed.ncbi.nlm.nih.gov/25765295/
- Luque A, et al. Botulinum toxin in the treatment of rosacea-associated facial erythema and flushing: A case report. Dermatologic Surgery. 2021. DOI: 10.1097/DSS.0000000000003167. https://pubmed.ncbi.nlm.nih.gov/33841616/
- Zhang M, et al. Safety and efficacy of botulinum toxin type A in treating erythematotelangiectatic rosacea: A systematic review and meta-analysis. Dermatologic Therapy. 2020. DOI: 10.1111/dth.13946. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096341/
- Calvisi L, et al. Botulinum toxin for treating facial erythema and flushing in rosacea: A systematic review and meta-analysis. Dermatology and Therapy. 2021. DOI: 10.1007/s13555-021-00578-w.
- Bharti J, et al. Botulinum toxin type A in the treatment of facial erythema in rosacea. Journal of Cutaneous and Aesthetic Surgery. 2018. DOI: 10.4103/JCAS.JCAS_53_18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096341/
- Mi X, et al. Intradermal botulinum toxin A injection for facial erythema associated with rosacea: A prospective pilot study. Journal of Drugs in Dermatology. 2022. DOI: 10.36849/JDD.2022.6334. https://pubmed.ncbi.nlm.nih.gov/25548852/
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