Efficacy and safety of intense pulsed light in rosacea: A systematic review

Introduction

Rosacea is a chronic inflammatory cutaneous disorder affecting the face, especially the cheeks, chin, nose and forehead.^1,2 Cutaneous signs of rosacea include flushing, erythema, telangiectasia, oedema, papules, pustules and rhinophyma.³ More than 50% of patients with rosacea also experience ocular symptoms such as dryness, irritation, blepharitis, conjunctivitis, and compromised vision.⁴ It is more common in women and its prevalence varies across populations, ranging from less than 1% to 22%.⁵

The pathophysiological mechanisms of rosacea are unclear, but they involve genetic factors, vascular and neural abnormalities, dermal matrix degeneration, microorganisms and environmental factors, such as heat, nutrition and ultraviolet light.^2,6 The inflammatory process in the skin may be worsened by pro-inflammatory substances and degradative enzymes released by inflammatory cells, leading to dermal destruction.⁷

The primary focus of rosacea treatment is to alleviate symptoms and improve facial appearance. Educating patients about their skin condition and potential exacerbating factors is an important aspect of management. This helps them identify and avoid triggers that can worsen their condition.^3,8 Beta-blockers, α2-adrenergic agonists and brimonidine tartrate are frequently used pharmacological interventions.^3,7,9

Various light-based therapies such as low laser therapy and intense pulsed light (IPL) have been used for treating the erythema and telangiectasia of rosacea.^8,3 IPL uses non-collimated, non-coherent light of different wavelengths to target specific chromophores making it a versatile therapy for hair removal, skin rejuvenation and the treatment of pigmented or vascular lesions.¹⁰ The 577 nm wavelength of IPL corresponding to the third absorption peak of oxyhaemoglobin is absorbed by haemoglobin inducing photothermolysis. This selectively destroys blood vessels and causes thermal damage to the papillary and upper reticular dermis.^11,12 IPL destroys abnormal vessels in patients with rosacea and improves the dermal connective tissue disorganisation of the vascular component of rosacea (erythema and telangiectasia).^13,14

While the positive effects of IPL in treating rosacea are well-documented, its use is still controversial, particularly with regard to the parameters required to achieve optimal results. Despite advances in research on the use of light for managing rosacea, no systematic review of the exclusive use of IPL in rosacea has been conducted. The present study aimed to analyse literature on the effects and safety of IPL for treating rosacea-related symptoms in clinical studies.

Materials and Methods

This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines¹⁵ at the Federal University of the State of São Paulo, Brazil in October 2022. It was registered on the online International Prospective Register of Systematic Reviews (PROSPERO) of the National Institute for Health Research (Registration ID: CRD42021285751).

We used the Medline, PubMed and Scopus electronic databases to systematically search for articles on IPL and rosacea in clinical trial studies. The Medical Subject Headings (MeSH) terms and Boolean operator in the electronic search strategy were “intense pulsed light” and “rosacea”. Articles were selected based on their titles and abstracts meeting the eligibility criteria. The methodological quality of all included studies was assessed using the Cochrane Risk of Bias (RoB 2.0)¹⁶ scale for randomised clinical trials and Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I).¹⁷

Results

The flow diagram shown in Figure 1 illustrates the search strategy used in the study. A total of 233 articles were retrieved from the Scopus and PubMed databases (147 and 86 articles, respectively). After excluding 64 duplicated records, 134 articles were excluded after reading the title and 8 after reading the abstract. The remaining 27 full-text articles were assessed for eligibility and finally 14 studies were selected for the systematic review. The classification of rosacea was not a criterion for the inclusion/exclusion of studies.

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Figure 1:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of the studies included in the systematic review.

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The general characteristics of patients and experimental groups from these 14 articles are summarised in Table 1. The studies included patients with Fitzpatrick skin types I to IV, with ages ranging from 15 to 78 years. Three studies recruited only females.^18,19,20 While 11 studies recruted both male and female patients.^{12,13,21–29}

All studies used IPL alone as an intervention group. Ten studies did include any control groups.^{13,18–20,23–28} three studies^12,20,28 used a group of pulsed dye laser (PDL) treated patients and 1 study used untreated patients as controls.²⁹ In the study conducted by Neuhaus et al.,²⁹ patients were treated with IPL on one side of the face and PDL on the other.²⁹

The IPL protocols used in the studies are detailed in Table 2. Spot sizes were mentioned in 7 studies and varied from 1 × 4 mm to 15 × 40 mm.^{19,20,22–24,26,28} The pulse duration was specified in all studies and varied from 1.5 to 25 ms and the wavelengths used ranged from 420 to 1200 nm. In 4 studies, 2 separate handpieces emitting different wavelengths were used [Table 2].^20,23,27 The energy density applied also varied widely from 15 J/cm² to 90 J/cm².

Various evaluation methods were employed to assess the effects of IPL [Table 3]. All studies used digital photography to assess the area of telangiectasia, erythema, and the number of lesions.^{12,18,20–23,25,26,28,29} Blood flow analysis was used in one study,¹⁸ while two studies used spectrophotometer analysis.^19,29 Questionnaires and scales employed in these studies included various visual analogue scales (4, 5, 6, and 10 point VAS) and patient global assessment (PGA).

The positive effects of IPL persisted after treatment in all the studies. The area of telangiectasia and erythema as well as the number of lesions were significantly reduced after treatment.^{18,20–26,28,29} Kassir et al.²⁶ observed that 80% of patients had reduced redness, 78% noted reduced flushing and improved skin texture, 72% reported fewer acneiform breakouts, and 51% demonstrated a reduction in telangiectasias. Tirico et al.¹² noted decreased redness after IPL treatment, Marques et al.²⁸ observed improvement in flushing and skin texture and Kim et al.²¹ observed clinical improvement in erythema, telangiectasia, papules, and pustules. Improvement after IPL treatment was demonstrated by spectrophotometer analysis in two studies.^19,29

Improvement in signs and symptoms after IPL treatment were confirmed through the use of scales and questionnaires. In the study of Campolmi et al.²⁵ Neuhaus et al.²⁹ noted an improvement in patient-rated signs and symptoms.

Adverse effects were transitory and included pain, oedema, minimal bruising, and burning sensations.

The risk of bias assessment for both the randomised and non-randomised trials is illustrated in Figures 2a and 2b. The RoB-2 assessment [Figure 2a] revealed an unclear risk of bias in all studies due to missing outcome data. This arose from the randomisation process in 3 studies and in the measurement of the outcome in one study. A high risk of bias was noted in one study due to deviations from intended interventions²⁹ and in 2 studies in the bias domain in selecting the reported result.^12,21 A low risk of bias arising from the randomisation process was noted in a single study,²⁹ in 2 in the selection of the reported result,^22,29 and in 3 studies each due to the deviations from intended interventions^12,21,22 or in the measurement of the outcome.^21,22,29

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Figure 2a:

Risk of bias assessment for the randomised clinical trials (RoB-2).

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Figure 2b:

Risk of bias assessment for the non-randomised intervention studies (ROBINS-I).

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In the ROBINS-I assessment [Figure 2b], one study had a high risk of bias in the field of measurement of outcomes.²⁶ Additionally, an unclear risk of bias was found in the domains of deviations from intended interventions,²⁶ missing data,²⁴ and measurement of outcomes.²³ All studies had a low risk of bias classification in the domains of confounding, selection of participants, type of interventions, and selection of the reported result.

Discussion

IPL is an effective non-invasive therapeutic intervention for the treatment of port wine stains, haemangiomas, and facial telangiectasia.^30,31,32 It has also been demonstrated to reduce erythema, papules and pustules and improve skin texture in patients with rosacea.^33,34 Multiple sessions (up to 15) at 1-to-3-week intervals may be necessary, and parameters need to be adjusted individually according to the phototype, severity and tolerance to minimise side effects.²⁶

Our systematic review found that IPL was effective in managing the symptoms of rosacea in both males and females of Fitzpatrick skin types I to IV aged between 15 and 78 years. However, due to the wide range of IPL parameters used in these studies (wavelengths varying from 420 nm²⁶ to 1200 nm,²³ energy density from 15 J/cm² to 90 J/cm²,²³ and number of sessions from 1 to 7)^23,26, and the different methods used to evaluate the effects of IPL (digital photos, patient self-reported perception, scales, and questionnaires), the end results are not strictly comparable.

The optimal use of IPL parameters such as fluence, pulse duration, wavelengths, treatment time, and spot size in clinical settings is crucial for achieving the best tissue responses and minimising the risk of tissue damage.^31,35 Shorter wavelengths (400 to 585 nm) and shorter pulse durations (450 ms) are thought to have a better effect on skin owing to the limited depth of penetration (up to 1.5 mm).³³

Papagerogiu et al, using a 560 nm a wavelength observed an average reduction of 3.5 points in the severity of rosacea pain measured with the 10-point VAS.²⁴ In this same study, over 50% improvement was seen in 73% and 83% of patients as per the evaluation of the patients and physicians respectively. The results were sustained for 6 months. Other authors used higher wavelengths (e.g., 1200 nm) and also noted good results.³⁰ These effects may be due to the absorption of wavelengths in the 900 to 1200 nm spectrum by water in the dermis triggering a cytokine reaction that stimulates the formation of elastin and collagens I and III.

A wide range of energy densities (from 15 J/cm² to 90 J/cm²) were used in the studies. High energy densities can cause burns, while lower fluences may not be effective.³⁶ The spot size (area covered by the beam at the tip of the applicator) varied significantly among different machines, ranging from 4 to 64 mm².^20,28,37 The number of treatment sessions and the period of treatment were not uniform across the studies and between 1 and 7 treatment sessions at intervals of 3 to 4 weeks were used. Although standard IPL protocols suggest a 3–4 week interval between treatments, Papageorgiou et al. have proposed that a longer interval of 6 or 8 weeks may be more cost-effective.²⁴

Most studies have reported an improvement in erythema and telangiectasia after IPL application.^30,38–44 This may be due to the ablation of abnormally dilated vessels and the reduction of extravascular leakage of inflammatory mediators.¹³ IPL also stimulates new collagen deposition and collagen remodelling, which improves support for small blood vessels, dermal connective tissue disorganisation, and elastosis.^23,24 The improvement in the vascular features of rosacea (erythema and telangiectasia) could subsequently lead to a decrease in inflammatory lesions.^23,24,32

Limitations

Eight of the studies were of low methodological quality.^{18,19,23–28} Neither the investigators nor the subjects were blinded, and the treatments were not concealed.

Conclusion

IPL is a safe and effective treatment for rosacea. However, since all trials included in the studies show methodological limitations, more trials of better methodological quality must be conducted.