Beyond Ultraviolet: A Scoping Review of Light Treatments in Atopic Dermatitis

Abstract

Phototherapy has been long recognized as a useful tool in dermatology, and while UV therapy has proven to be successful in many conditions, other forms of light therapy also have positive evidence of efficacy for skin conditions, including atopic dermatitis (AD). The purpose of this review is to examine the existing literature using light as a treatment for AD in humans, outside of conventional UV phototherapy. Literature search of databases and search engines Embase (Elsevier), Web of Science (Clarivate), Pubmed (NLM/NIH), CINAHL (EBSCO), and Google Scholar was performed. Fifteen studies were found: 8 investigated heliotherapy and climatotherapy, 4 examined blue light therapy, and the remaining 3 examined other forms of light therapy such as low-level laser therapy, intense pulsed light therapy, and pulsed-dye laser treatment. The studies found were heterogeneous and this heterogeneity severely limits more nuanced meta-analysis or more definitive conclusions. Light therapy appears to be extremely promising in treating AD and despite its long history, continues to evolve. Non-UV forms of light are particularly notable for the treatment of AD due to their lower risk profile. This article highlights the potential of these therapies and the need for continued research to obtain a homogenous body of literature that can inform clinicians in their practice.

Capsule Summary

Non-UV forms of light therapy have positive evidence of efficacy for skin conditions, including atopic dermatitis (AD).

Almost all studies investigating therapies such as heliotherapy and climatotherapy, blue light therapy, low-level light therapy, intense pulse light therapy, and pulsed-dye laser treatment resulted in statistically significant improvement of AD.

However, the studies found were heterogeneous and more research in this field is needed. Nonetheless, these therapies hold much promise.

INTRODUCTION

The term “phototherapy” derives from the ancient Greek word “photos” meaning light, and it refers to the practice of using light as a healing modality. Light has many forms, including visible light from 380 to 700 nm, as well as many wavelengths invisible to the human eye. These wavelengths include gamma rays, X-rays, ultraviolet (UV) light, and the rest of the electromagnetic spectrum.¹

Phototherapy has been long recognized as a useful tool in dermatology, showing effective results for many conditions from vitiligo to psoriasis.^2-4 In 1903, the Danish physician Niels Ryberg Finsen won the Nobel prize in medicine for his groundbreaking work on the therapeutic uses of light. The mechanism of action of this therapy is likely due to the disruption of inflammatory cells, the induction of apoptosis, and the reduction in production of cytokines.^5,6 Specifically, phototherapy has been shown to induce T-cell apoptosis as well as decrease inflammatory cytokines such as interleukin-5 (IL-5) and IL-13.^7,8

The benefits of phototherapy similarly extend to atopic dermatitis (AD). This condition is characterized by inflammation, a disruption of the skin barrier, an altered skin microbiome, and transepidermal water loss.⁹ Phototherapy is thought to help by reducing the inflammation and promoting differentiation of keratinocytes to accelerate the healing of the skin barrier.⁴ Furthermore, UV light has been shown to decrease Staphylococcus aureus, as well as increase filaggrin levels in the skin.^10,11

Within UV therapy there are a variety of treatments such as UVA, broadband UVB, narrowband UVB, and excimer laser that have been studied and are well-established. While these therapies are generally considered safe they also have some associated risks. UV light has been associated with burns, photoaging, erythema and skin damage, and over time, an increased risk for skin cancer.^12,13

While UV therapy has proven to be successful in many conditions, other forms of light therapy also have positive evidence of efficacy for skin conditions, including AD. The purpose of this review is to examine the existing literature using light as a treatment for AD in humans, outside of conventional UV phototherapy.

METHODS

Structured searching of the literature databases Embase (Elsevier), Web of Science (Clarivate), Pubmed (NLM/NIH), and CINAHL (EBSCO) formed the primary literature corpus. An additional search of the search engine Google Scholar was also performed. Searches included all dates and languages. Search terms included both indexed and keyword terms for AD and various light therapies, including specific light spectra, phototherapy, and laser therapies. Full search strategies are included in the appendix. All search results from databases were uploaded into Covidence (covidence.org. Melbourne, Australia). The first 200 results from Google Scholar were uploaded (see Fig. 1).

Figure 1.

Prisma diagram.

Final determination of the included studies was determined by a two-step screening process using Covidence software. An initial 50 study random screen was conducted by both A.C.Z. and P.L. to ensure agreement on screening terms. Afterward, a two-step screening process was performed by A.C.Z. reviewing titles/abstract and full text reviews and P.L. was consulted in cases of uncertainty. Then, A.C. included articles if they were English language articles, studies where the intervention was non-UV therapy, conducted with human subjects and that examined AD. Studies were rejected if they were case reports or literature reviews, commentary, non-English language articles, studies where the intervention included artificial UV, studies conducted on animals or in vitro (i.e., human cell lines) or not examining AD.

Included articles were exported and analyzed in excel. Research studies were categorized by therapy type and analyzed and described by study type, population, length and type of intervention, and outcomes.

RESULTS

Our search concluded with 15 studies, 8 of which investigated heliotherapy and climatotherapy, 4 of which examined blue light therapy, and the remaining 3 examined other forms of light therapy such as low-level laser therapy (LLLT), intense pulsed light (IPL) therapy, and pulsed-dye laser (PDL) treatment.

Heliotherapy and Climatotherapy

Both heliotherapy and climatotherapy are based on using natural sunlight to treat disease and the terms are commonly used interchangeably. The difference between these two therapies is that heliotherapy refers solely to the sun and, while climatotherapy involves the sun in addition to certain climates and maritime proximity.¹⁴ These therapeutic modalities were the initial forms of treatment that were used to examine the use of light in treating AD.

Five of these studies involved the relocation of patients for treatment in the Canary Islands, the Dead Sea, or to the patients summer homes in Montenegro. For either 2–4 weeks, these patients benefited from the increased sun of these geographies. All of these studies found that patients who traveled to these locations had significantly reduced Scoring atopic dermatitis (SCORAD) values, and that these remained significantly decreased after the completion of treatment.^{15B16 -19} Out of these studies, one of them showed a significant decrease (P < 0.0001) in the use of steroid treatment compared with the baseline. In addition, a study was conducted as a follow-up to Kudish et al., which showed a reduction of steroid use after heliotherapy.²⁰ In this study, less than 25% of patients in the group who had traveled to the Dead Sea to receive therapy were using topical steroids at all but one evaluation in the 18-month follow-up period.

Other studies that examined exposure to sunlight therapy further supported the benefits of this treatment. For example, a study using full-spectrum light therapy (FSL), an artificial light source that mimics the wavelengths of natural sunlight (including UV), found beneficial results. This randomized-controlled trial found that the FSL-irradiated group had significantly improved SCORAD (P < 0.01) as well as eosinophils, IL-4, and IL-5 (P < 0.001) compared with the control group.²¹ In a similar fashion, a questionnaire regarding sun exposure, found that sunlight was considered beneficial for more than half (59.6%) of patients. Furthermore, a third of patients (33.3%) reported the improvement of AD during summer vacations (Table 1).²²

Table 1.

Studies Examining Heliotherapy and Climatotherapy in Atopic Dermatitis

Study	Year	Design	Population	Length	Intervention	Outcome
Autio et al¹⁵	2002	Cohort	n = 26 adults with moderate to severe AD	2–3 weeks	Treatment in the Canary Islands	SCORAD was significantly reduced 2 weeks after therapy (P < 0.0001) and remained reduced 3 months after (P < 0.0001) There was no significant difference between SCORAD between patients receiving 2 versus 3 weeks of therapy 3 months after treatment, use of topical corticosteroid creams was significantly lower (P < 0.0001) compared with pretreatment
Karppinen et al¹⁶	2015	Cohort	n = 13 patients with unspecified degree of AD	2 weeks	Treatment in the Canary Islands	PO-SCORAD decreased significantly from baseline (P < 0.001). Using the VAS scores, there was significant improvement in disease severity and pruritus (P < 0.001) at week 2. QoL was improved showing a significant decrease in mean DLQI score (P < 0.001) in AD patients After 3 months, PO-SCORAD and DLQI remained significantly improved (P = 0.002), whereas VAS did not remain significantly decreased
Karppinen et al¹⁷	2017	Cohort	n = 60 patients with unspecified degree of AD	2 weeks	Treatment in the Canary Islands	DLQI scores decreased significantly from the baseline (P < 0.001) at the end of the study, and remained significantly decreased (P < 0.001) 3 months after therapy VAS showed a significant decline in disease severity and pruritus (P < 0.001) at the end of treatment and at the 3-month follow-up
Kudish et al¹⁸	2016	Cohort	n = 72 < 19 y/o with moderate to severe AD	4 weeks	Treatment in the Dead Sea	SCORAD immediately after therapy for 63 patients was 87.5 ± 13.4%. Three months later, the average SCORAD still had an overall average improvement of 71.3 ± 21.3% 3 months after completion of treatment, average SCORAD improvement for all patients 3 months later exceeded 70%, showing a decrease of <20% during this period
Terzic et al¹⁹	2023	Cohort	n = 24 > 18 y/o with moderate to severe AD	2 weeks	Treatment in Montenegro	There was a statistically significant reduction in SCORAD, EASI, SPS, and DLQI after 2 weeks of treatment (P < 0.001). All of these values remained significantly decreased at 3 months after therapy (P < 0.001)
Marsakova et al²⁰	2020	Nonrandomized controlled trial	n = 116 < 19 y/o moderate to severe AD	18 months	Therapy from Kudish et al. versus regular treatment of steroid cream	The overall average improvement in SCORAD was relatively constant, between 76% and 87% for the treatment group and between 82% and 88% for the control group. In the intervention group, none but two patients used topical steroids during the first 3 months. During the 18-month follow-up study, less than 25% of patients in the intervention group were using topical steroids at each evaluation, except for a peak usage with 31.9% at the 9-month follow-up
Byun et al²¹	2011	RCT	n = 38 > 18 y/o with moderate to severe AD	4 weeks	FSL versus emollient	In the FSL-irradiated group, SCORAD decreased significantly at week 4 (P < 0.01) and reduced further to at week 8. In the control group, mean SCORAD values did not change significantly during the entire study period (P = 0.236) FSL-irradiated group, the mean values of serum eosinophil, IL-4 and IL-5 counts showed a significant decrease at week 8 compared with baseline values (P < 0.001)
Napolitano et al²²	2020	Cross sectional	n = 114 > 18 y/o with unspecified degree AD	n/a	Questionnaire regarding sun exposure	There was no difference for days per year of sunlight exposure between persistent and adult-onset AD. Sunlight effect was considered beneficial for 59.6% of patients. 33.3% of patients reported the improvement of AD and 26.3% the complete resolution of the disease during summer vacations.

AD, atopic dermatitis; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; FSL, full-spectrum light; PO-SCORAD, Patient-Oriented Scoring Atopic Dermatitis; RCT, randomized controlled trial; SCORAD, Scoring Atopic Dermatitis; SPS, Skin Pruritus Scale; UVR, ultraviolet radiation; VAS, visual analog scale.

Blue Light Therapy

Light-emitting diodes (LEDs) can emit different wavelengths of light, including the UV spectrum. Our search results returned specifically blue LED light, which can be found between 400 and 500 nm. Blue light has been shown to improve hyperproliferative and inflammatory disorders, by acting on different molecules and modifying cell signaling pathways. Although the exact mechanism is not yet understood, blue light has been shown to decrease the proliferation of keratinocytes, increase the production of nitric oxide and reduce immune cell activation.²³

Out of the four studies retrieved using blue light for AD, three found significant decreases in disease severity. Severity was significantly reduced at different time points across studies: one was decreased as soon as visit 4 (P = 0.0152) and 5 (P = 0.0115).²⁴ Another was decreased at the end of 10 sessions, (P < 0.00001), and finally, one as late as 3 and 6 months (P < 0.005 and P < 0.002).^25,26 Only one study found no significant decrease in SCORAD in the treatment group.²⁷

All of the studies found a significant decrease in the incidence or severity of one or more symptoms. Although interestingly, in one study examining 450 nm versus 415 nm versus control, found that pruritus was only reduced at one wavelength. Itching was only significantly reduced in the 450 nm arm compared to control (P = 0.023), and this difference was not significant in the 415 nm group.²⁷ Blue light shows promise in treating AD, and in particular wavelengths above 450 nm appear to be more effective (Table 2).

Table 2.

Studies Examining Blue Light Therapy in Atopic Dermatitis

Study	Year	Design	Population	Length	Intervention	Outcome
Sadowaska et al²⁵	2024	Cohort	n = 20 patients with moderate to severe AD	10 sessions	453 nm light	After 10 sessions of full blue light therapy significant improvements were observed in EASI (P = 0.00016), SCORAD (P < 0.00001), VAS (P = 0.00251), and DLQI (P = 0.00351) Furthermore, pruritus was significantly improved (P < 0.00001)
Keemss et al²⁴	2016	RCT	n = 21 > 18 y/o with mild to moderate AD	4 weeks	453 nm light versus control, contralateral lesion (moisturizer cream)	The difference in the improvement between the treated and control areas was statistically significant at visit 4 (P = 0.0152) and 5 (P = 0.0115) There was a significant difference in CfB between the treated and control lesions (P = 0.0166) for ESI 1–4 but not for ESI 5–15. Erythema (P = 0.021), induration/papulation/edema (P = 0.042), and lichenification (P = 0.010) were significantly more reduced in the treated area at different visits
Becker et al²⁶	2011	Cohort	n = 36 > 18 y/o patients with severe, chronic AD	2–3 weeks	400–500 nm full body irradiation	At 3 and 6 months after treatment initiation, disease severity was significantly decreased (P < 0.005 and P < 0.002). Itching was already reduced after 15 days of treatment (P < 0.05), which became highly significant after 3 and 6 months (P < 0.002). Sleeplessness also decreased significantly over time (P < 0.002 at m3 and m6) DLQI significantly improved during treatment (P < 0.005)
Buhl et al²⁷	2023	RCT	n = 87 > 18 y/o patients with unspecified degree AD	8 weeks	450 nm light versus 415 nm light versus control (sham)	There was no significant decrease in the EASI or SCORAD between baseline visit and end of treatment in any groups in any of the treatment arms. Patients treated with 450 nm reported significant reductions in pruritus compared to control (P = 0.023). However, this difference was not significant in the 415 nm group.

AD, atopic dermatitis; CfB, change from baseline; DLQI, Dermatology Life Quality Index; EASI, Eczema Area and Severity Index; ESI, Erythema Severity Index; RCT, randomized controlled trial; SCORAD, Scoring Atopic Dermatitis; VAS, visual analog scale.

Other Light Therapies

The remaining studies examined other forms of light therapy such as LLLT, IPL therapy, and PDL treatment.

LLLT can use either lasers, LED light, or both forms by exposing cells to low level light, typically in the red or near infrared range. This therapy appears to be effective at reducing inflammation and stimulating healing.²⁸ This is achieved by stimulating cellular repair pathways, altering transcription factors such as Nuclear factor erythroid 2-related factor 2 (Nrf2) or Vascular endothelial growth factor (VEGF). In one study, LLLT was found to reduce skin symptoms in 62% of cases by more than 5 points in scales created by the investigators. Moreover, LLLT was found to reduce itching in 79% of cases by more than 1 point in scores created by the investigators. Both of these tools were created by the investigators and based on a 0–3 scale for each symptom (5 total symptoms) in addition to itch.²⁹ However, given the lack of P values in this study, it is impossible to discern whether these results were statistically significant.

IPL therapy uses different flashlamps and cutoff filters, which leads to the emission of light that can be anywhere between 500 and 1300 nm. IPL can adapt the wavelength, duration, and other characteristics to depending on the disease targeted.³⁰ In AD, IPL significantly decreased severity score and Dermatology Life Quality Index (DLQI) (P = 0.005). In addition, several symptoms were significantly improved, which included scaling (P = 0.003), erythema (P = 0.009), and lichenification (P = 0.008).³¹

Finally, PDL uses yellow light (typically in the 585–595 nm range) that can selectively destroy target vessels and tissue with minimal collateral damage.³² PDL has been shown to decrease inflammatory lesions, as well as cell proliferation through thermolysis.³³

This therapy decreases inflammation by suppressing keloid proliferation as well as other growth factors such as TGF-β1.³⁴ When used for AD, severity scores were significantly decreased after 2 and 6 weeks (P = 0.003 and P = 0.002, respectively). In addition, at 6 weeks, there was also a greater improvement of visual analog scale (VAS) in treated lesions compared to control (P = 0.003; Table 3).³⁵

Table 3.

Studies Examining Other Light Therapies in Atopic Dermatitis

Study	Year	Design	Population	Length	Intervention	Outcome
Morita et al²⁹	1993	Cohort	n = 112 patients with unspecified degree AD	One session	Low-level laser therapy	In 62% of cases, skin symptom scores decreased more than 5 points after therapy In 79% of cases, itching scores decreased more than 1 point after therapy After therapy, HLA-DR positive dendritic cells as well as HLA-DR positive dermal infiltrating cells decreased remarkably and ICAM-1 expression on keratinocytes and dermal infiltrating cells almost disappeared.
Oh et al³¹	2010	Cohort	n = 11, >12 y/o with mild to moderate AD	2 weeks	Intense pulsed light therapy	The ESS was significantly lower 4 weeks after the third treatment (P = 0.005). Scaling (P = 0.003); edema, induration, and papules (P = 0.011); erythema (P = 0.009), and lichenification (P = 0.008) improved significantly. Mean DLQI score improved from baseline to 4 weeks after the last treatment (P = 0.005)
Syed et al³⁵	2008	Nonrandomized controlled trial	n = 12 < 18 y/o	One session	Pulsed-dye laser treatment versus cooling treatment	After 2 and 6 weeks, the mean ESS decreased significantly in the treated lesions compared to control sites (P = 0.003 and P = 0.002, respectively). At 6 weeks, there was also a greater improvement of VAS in treated lesions compared with the control (P = 0.003)

AD, atopic dermatitis; DLQI, Dermatology Life Quality Index; ESS, Eczema Severity Score; HLA-DR, human leukocyte antigen-DR; ICAM-1, intercellular adhesion molecule-1; VAS, visual analog scale.

DISCUSSION

Light, in all its forms, appears to be a promising treatment for AD, from more established therapies to newer ones. However, it is important to note some of the differences in the studies compared in this review. First, the study design varied immensely, from a questionnaire to randomized controlled trials. Many of the studies included did not have control groups and relied on a patient’s change from baseline to declare whether a result was significant or not. In addition, there was variation in the initial disease severity studied: some were limited to mild or moderate disease, while others looked at moderate to severe, and a few did not specify severity. Finally, the protocols in these studies differed regarding whether subjects were allowed, discouraged, or completely banned from using other treatments such as topical corticosteroid preparations. This heterogeneity severely limits more nuanced meta-analysis or more definitive conclusions.

In addition, there is tremendous variability of accessibility and cost of these approaches. For example, while treatments where patients traveled to warmer climates were highly effective, it is costly and time-consuming for individuals to do so. While sunlight appears to be an effective therapy for AD, many patients living in less sunny geographies are unlikely to be able to reap such benefits. Similarly, laser therapy can be costly and many patients would not be able to receive this treatment regularly. However, LED does appear to be more easily accessible to patients, with many different products existing for at home treatment with blue and red LED light. Surprisingly, none of the studies in our search resulted in studies looking at red LED light therapy, which has previously shown to be beneficial in other skin conditions.³⁶

It is important to remember that overexposure to any of these therapies can be harmful. Heliotherapy and climatotherapy carry the risk associated with UV exposure, such as erythema, blistering, and chronically, skin cancer.³⁷ Conversely, it has been posited that blue light can induce reactive-oxygen species in the skin that can lead to oxidative stress leading to skin aging and hyperpigmentation.²³ UV-free therapies appear to be safer given the lack of potential carcinogenic effects. Of the studies examined, none reported serious adverse side effects. However, it should be noted that most of these studies excluded Fitzpatrick I skin type, which is typically most sensitive to light. In addition, none of these studies examined the long-term side effects of these therapies.

CONCLUSION

Overall, light therapy appears to be extremely promising in treating AD and despite its long history, continues to evolve. Non-UV forms of light are particularly notable for the treatment of AD due to their lower risk profile. However, due to the heterogeneity of the studies currently available, it is difficult to understand exactly how these therapies can be used in clinical practice. This article highlights the necessity for more research and homogenous studies to better assesses the potential these novel therapies hold.

Footnotes

AUTHORS’ CONTRIBUTION

P.L.: Conceptualization, investigation, writing—review and editing, supervision, and validation. T.G: Methodology, investigation, and writing—original draft. A.C.Z.: Investigation, and writing—original draft.

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