
==== Front
Dermatol Ther (Heidelb)
Dermatol Ther (Heidelb)
Dermatology and Therapy
2193-8210
2190-9172
Springer Healthcare Cheshire

39180711
1248
10.1007/s13555-024-01248-3
Brief Report
Prospective Clinical Study: Full-Body Blue Irradiation in the Treatment of Atopic Dermatitis
http://orcid.org/0000-0002-8828-6976
Sadowska Magdalena magdalena.sadowska.umed@gmail.com

1
Narbutt Joanna 1
Nolberczak Daniel 1
Ciążyńska Magdalena 1
Skibińska Małgorzata 1
Sobolewska-Sztychny Dorota 12
Aubert David 3
Lesiak Aleksandra 12
1 https://ror.org/02t4ekc95 grid.8267.b 0000 0001 2165 3025 Department of Dermatology, Pediatric Dermatology and Dermatological Oncology, Medical University of Lodz, Kosciuszki 4, 90-419 Lodz, Poland
2 https://ror.org/02t4ekc95 grid.8267.b 0000 0001 2165 3025 Laboratory of Autoinflammatory, Genetic and Rare Skin Disorders, Department of Dermatology, Paediatric Dermatology and Oncology, Medical University of Lodz, Lodz, Poland
3 Phlecs, High Tech Campus 12, 5656 AE Eindhoven, The Netherlands
24 8 2024
24 8 2024
9 2024
14 9 26312643
7 3 2024
29 7 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
Introduction

Ultraviolet-free (UV-free) blue light phototherapy has emerged as a promising option due to its reported efficacy and minimal adverse effects. This study aims to evaluate the effectiveness of full-body blue light irradiation in both adult and pediatric patients with atopic dermatitis (AD), assessing its impact on skin condition and mood regulation by investigating serum concentrations of serotonin and kynurenine pathway metabolites.

Methods

20 patients (age 9–45) with moderate and severe AD were included in the study. Treatment consisted of 10 irradiations with Full Body Blue device (453 nm). Serum concentrations of serotonin, quinolinic acid, kynurenic acid, tryptophan, and kynurenine were measured before and after irradiations.

Results

After 10 sessions of full blue light therapy (453 nm) statistically significant improvements were observed in Eczema Area Severity Index (EASI 13.16 vs. 8.65; p = 0.00016), SCORing Atopic Dermatitis (SCORAD 44.99 vs. 23.73; p < 0.00001), Visual Analogue Scale (VAS 6.53 vs. 3.95; p = 0.00251), 10-item pruritus severity scale (13.32 vs. 7.05; p < 0.00001). Moreover, statistically significant decrease in Dermatology Life Quality Index (DLQI) was noted (14.37 vs. 7.42; p = 0.00351). Additionally, increase in the serum concentration of serotonin was observed after completing 10 irradiation sessions (median 139.77 mg/ml vs. 274.92 mg/ml; p < 0.00001).

Conclusion

Blue light may be a promising and safe treatment in patients with AD. It might also positively influence mood. Further investigations are needed to confirm those findings.

Trial Registration

ClinicalTrials.gov identifier, NCT06516783.

Keywords

Atopic dermatitis
Blue light
Mood regulation
Serotonin
This research was funded by statutory activities of Medical University of Lodz no. 503/1-064-01/503-11-001.issue-copyright-statement© Springer Healthcare Ltd., part of Springer Nature 2024
==== Body
pmcKey Summary Points

Why carry out this study?	
Both topical and systemic treatments in atopic dermatitis (AD) pose the risk of developing adverse effects, blue light therapy might be a possible alternative with high safety profile.	
The aim of this study was to assess the effectiveness of full body blue irradiations in the treatment of AD in adult and pediatric populations. Furthermore, we aimed to investigate whether blue light had an impact on serum concentrations of serotonin and kynurenine pathway metabolites involved in mood regulation.	
What was learned from the study?	
After 10 sessions of full blue light therapy statistically significant improvements were observed in Eczema Area Severity Index (EASI 13.16 vs. 8.65), SCORing Atopic Dermatitis (SCORAD 44.99 vs. 23.73), Visual Analogue Scale (VAS 6.53 vs. 3.95), 10-item pruritus severity scale (13.32 vs. 7.05), Dermatology Life Quality Index (DLQI 14.37 vs. 7.42) and statistically significant increase in the serum concentration of serotonin was observed (median 139.77 vs. 274.92 mg/ml).	
Blue light seems to be a promising and safe treatment in patients with AD and might enhance mood, but further investigations are needed to confirm these findings.	
Blue light could be a possible therapy for patients with contraindications to conventional therapies or as a combined therapy with conventional methods.	

Introduction

Atopic dermatitis (AD) is a common chronic inflammatory skin disease, typically manifesting in the early childhood. It is characterized by recurrent exacerbations and remissions. The localization of the skin lesions varies with age and is accompanied by severe pruritus and dryness of the skin. The pathogenesis of AD involves a complex interplay of genetic, environmental, and immunological factors, alongside an impairment of the epidermal barrier [1, 2]. Patients with AD experience significant decrease in their quality of life due to chronic pruritus, insomnia, social marginalization and the persistent nature of the condition. Treatment of AD always requires regular use of emollients. In mild AD, topical corticosteroids or calcineurin inhibitors are also used. In more severe cases, phototherapy—narrowband ultraviolet B (UVB) can be added to the treatment regimen. Severe AD is the indication for systemic immunosuppressive or immunomodulatory treatment [3, 4]. Both topical and systemic treatments pose the risk of developing adverse effects. Long-term use of ultraviolet radiation (UV) treatment may induce premature skin aging and increase the risk of carcinogenesis [5–9]. UV-free blue light phototherapy (400–500 nm) may be a promising alternative treatment method. Previous studies showed that blue light irradiation was not associated with the occurrence of serious adverse effects [10–18].

The mechanism of action of blue light is not fully understood and is the subject of scientific research. Chromophores (photoacceptors) such as opsins, flavins, porphyrins, nitrosated proteins and cytothrome c oxidase are involved in this process through nitric oxide mediated reactions and reactive oxygen species (ROS) formation [19–21]. There are studies suggesting its anti-inflammatory potential. Blue light irradiation (at the intensities 3.75, 7.5, 15 J/cm2) of dendritic cells resulted in lower secretion of interferon-gamma (IFN-γ), Interleukin-2 (IL-2), IL-10, IL-12p70, IL- 1β, and TNF-α (except IL-4) by stimulated T-cells. Interestingly, this effect was more pronounced at higher doses of blue light. Therefore, blue light might be beneficial in inflammatory skin diseases such as AD [22]. Moreover, in another study it was showed that blue light irradtiation lead to lower expression of inflammatory genes, probably because of stimulatation of steroid hormone biosynthesis [22]. There are only few studies evaluating the use of blue light therapy in patients with AD. Blue light used locally showed a significant improvement in atopic hand and foot eczema (10 patients, 30 min focal irradiations with partial body irradiation device, 3 times per week for 4 weeks; 40% of emission between 400 and 500 nm, 26% between 400 and 450 nm, 42 J/cm2)[10]. Furthermore, local blue light ((λ = 453 nm, 90 J/cm2) irradiation reduced severity of eczema lesions in 20 patients with atopic and nonatopic eczema [11]. Two studies evaluated full body blue irradiations in individuals with mild to moderate AD, while another study focused on severe cases of AD [12, 13]. Both of them showed a positive impact on pruritus, whereas only one observed significant Eczema Area Severity Index (EASI) decrease after irradiations. These studies were limited to adult patients. The aim of our study was to assess the effectiveness of full body blue irradiations in the treatment of AD in adult and pediatric populations. Furthermore, we aimed to investigate whether blue light had an impact on selected mood regulators including serotonin and kynurenine pathway metabolites. They are related to mood regulation. Previous research indicated a potential effect of blue light on β-endorphin production, which could also be linked to mood regulation [23]. Patients with AD are more susceptible to mood disorders and depression. Our goal was to investigate whether blue light irradiations would improve the skin condition, but also the mood of patients with AD.

Methods

The study was approved by Ethics Committee of the Medical University of Lodz (RNN/223/20/KE 08.09.2020). Consent to participate and publish the data was obtained from all the participants. The patients agreed to the publication of their images. This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments.

Twenty patients (age 9–45; 5 males and 15 females) with moderate and severe AD (EASI 13.16; range 6.2–19.4; SCORing Atopic Dermatitis—SCORAD 44.99; range 30.5–68.6) were included in the study from November 2020 to November 2022. Eligibility criteria were: a diagnosis of AD according to Hanifin and Rajka criteria ([24]), age above 8 years old and written informed consent. Excluded from the study were patients with known hypersensitivity to ultraviolet or blue radiation, patients under 8 years of age; women who were pregnant, breastfeeding or planning to become pregnant during the treatment; patients who participated in another experiment / clinical trial within 30 days prior to inclusion in the study; patients unwilling or unable to respect the requirements of the study; patients with other skin diseases, patients with planned hospitalizations or surgical procedures during the time of the study; patients using medications with proven phototoxic effect, patients with diastolic blood pressure > 95 mmHg and < 65 mmHg, patients with congenital or acquired immune disorders; patients with a history or at the time of the examination diagnosed with a skin cancer, severe actinic keratosis or dysplastic moles; patients diagnosed with genophotodermatoses with increased risk of skin cancers (including xeroderma pigmentosum, Cockayne's syndrome and Bloom's syndrome); patients addicted to alcohol or drugs in the last 12 months [Table 1].Table 1 Demographics and comorbidities

Patient	Age	Sex	Fitzpatrick type	Comorbidities	Medications	
1	12	F	II	None	None	
2	38	F	III	None	Antihistamines—cetirizine, hydroxyzini	
3	12	F	II	Asthma	Budesonidum inhalation, antihistamines—loratadinum	
4	12	F	III	None	Antihistamines—cetirizine, hydroxyzini	
5	16	F	II	Asthma	Antihistamines -cetirizini	
6	26	F	II	None	Ethinyloestradiolum, gestodenum, antihistamines: cetirizini, hydroxyzzini	
7	31	F	II	Allergic Rhinitis	Antihistamines: bilastinum	
8	26	F	II	Hypothyroidism, insulin resistance	Levothyroxinum natricum	
9	18	F	II	None	Antihistamines—rupatadinum	
10	28	M	III	None	Antihistamines—levocetirizine	
11	9	M	III	None (Asperger syndrome in susp.)	None	
12	24	F	II	None	None	
13	34	F	II	None	Antihistamines—bilastinum	
14	17	M	III	Depression	Fluoxetinum, quetiapinum	
15	38	F	II	None	None	
16	18	F	II	Allergic rhinitis	Antihistamines—levocetirizine	
17	20	M	II	None	None	
18	17	M	II	None	None	
19	39	F	II	None	Dienogest + ethinyloestradiolum	
20	45	F	II	Hypertension	Ramiprilum, acetylsalicylic acid	

Device

Full Body Blue GEN 1.0 device (built by PHLECS B.V., Phlecs, High Tech Campus 12, 5656 AE Eindhoven, The Netherlands) with European Community (EC) Certificate (number 2238613CE01) was used in the study. The device provides phototherapeutic light through light panel with treatment Light Emitting Diodes—LEDs (wavelength 453 nm, irradiance 40mW/cm2; dose 36 J for 15 min treatment) to one side of the body of the patient who is lying flat on an examination bed [Fig. 1]. All patients and personnel were wearing the protective eyewear (wavelength range (λ) 400–500 nm) at all times when the device was switched on.Fig. 1 Full Body Blue GEN 1.0 device

Study Plan

After giving written, informed consent, skin examination was performed (including photo documentation) and each patient had skin phototype assessed according to Fitzpatrick’s scale. A detailed medical history was collected. In addition, patients completed the Dermatology Life Quality Index (DLQI; 0–30 points) questionnaire and 10-item pruritus severity scale (3–20 points). Clinical assessment was performed using SCORAD (0–103 points), EASI (0–72 points) and Visual Analogue Scale (VAS; 0–10 points). On day 0, before the start of the treatment blood samples were collected to assess the serum concentrations of serotonin (5-hydroxytryptamine; 5-HT; mg/ml), quinolinic acid (mg/ml), kynurenic acid (mg/ml), tryptophan (mmol/l), and kynurenine (mmol/l). The study was scheduled for 10 irradiations session. Full body blue light was administered for 15 min to each side of the body of the patient (30 min in total) 3–5 times per week using the PHLECS Full Body Blue device. During the treatment patients were allowed to use emollients. Twenty four hours after the final irradiation, a control visit was performed to assess the effectiveness and safety of the therapy. The same parameters as for the first visit were used (DLQI, SCORAD, EASI, VAS, 10-item pruritus severity scale) and blood samples were collected. Photographic documentation was carried out at each visit [Table 2].Table 2 Study Protocol

DLQI Dermatology Life Quality Index, EASI Eczema Area Severity Index, SCORAD SCORing Atopic Dermatitis, EASI Eczema Area Severity Index, VAS Visual Analogue Scale

Blood for testing was collected from the elbow vein between 7.00 and 9.00 a.m, into appropriate test tubes, 8 ml each. After the blood had completely clotted at room temperature, the blood was centrifuged at 3000 revolutions per minute (RPM) for 10 min. The serum from above the clot was collected and portioned into Eppendorf tubes. All tested material was divided and deep-frozen to—70 ℃. Prior to conducting analysis, appropriate portions of the material were thawed and thoroughly mixed. The samples were never re-frozen. The concentration of serotonin in the serum was determined using a commercially available Enzyme-Linked Immunosorbent Assay—ELISA kit (IDK system Immunodiagnostik AG, Germany). The concentration of quinolinic acid and kynurenic acid in the serum was determined using ElISA kit (Cloud Clone Corp.). The concentration of tryptophan and kynurenine in the serum was determined using Indoleamine 2,3-Dioxygenase activity—IDO activity ElISA (Immunduer-grafik AG, Germany).

Statistical analysis was performed using Statistica 13 software. Characteristics of participants including demographic data and clinical assessments were presented as means with standard deviations or cumulative incidence (N) with percentages. Distribution of continuous variables was evaluated using the Shapiro–Wilk test. Student t-test or non-parametrical counterparts were used to compare 2 groups. For comparison of more than 2 groups Friedman ANOVA was employed. A p-value < 0.05 was deemed significant.

Results

Patients

Twenty patients with AD who met the inclusion criteria were included in the study (15 females, 5 males). At the initial appointment the median disease activity was moderate and severe (EASI 13.16; SCORAD 44.99), patients experienced moderate itching (VAS 6.53; 10-item pruritus severity scale 13.32) and moderately impaired quality of life (DLQI 14.37).

Clinical Response

After 10 sessions of full blue light therapy (administered 3–5 times per week), statistically significant improvements were observed in EASI (13.16 vs. 8.65; p = 0.00016; improvement by 34.35%), SCORAD (44.99 vs. 23.73; p < 0.00001; improvement by 47, 25%) and VAS (6.53 vs. 3.95; p = 0.00251; improvement by 39.51%). Furthermore, patients reported reduction in pruritus and statistically significant improvement in 10-item pruritus severity scale (13.32 vs. 7.05; p < 0.00001; improvement by 47, 11%) was noted. Moreover, another observation was the improvement in the quality of life. Statistically significant decrease in DLQI was noted (14.37 vs. 7.42; p = 0.00351; improvement by 48.36%).

Safety

No serious adverse effects were observed. The mild side effects consisted of itching and dryness (1 patient—5%) of the skin few hours after irradiations and a sensation of warmth during (2 patients—10%) the treatment, which disappeared after turning off the lamp and the end of irradiation. None of these symptoms led to discontinuation of irradiations. No other adverse effects were observed.

Serological Data

The serum concentrations of serotonin (mg/ml), quinolinic acid (mg/ml), kynurenic acid (mg/ml), tryptophan (mmol/l), and kynurenine (mmol/l) were examined in patients before and after 10 sessions of irradiation. A statistically significant increase in the serum concentration of serotonin was observed after completing 10 irradiation sessions (median 139.77 mg/ml vs. 274.92 mg/ml; p < 0.00001). The changes of the other serum parameters were statistically insignificant: quinolinic acid (median 48.08 mg/ml vs 45.07 mg/ml; p = 0.60942), kynurenic acid (67.32 mg/ml vs 60.62 mg/ml; p = 0.24883), tryptophan (81.52 mmol/l vs 70.84 mmol/l; p = 0.31383), and kynurenine (3.32 mmol/l vs 3.1; p = 0.98835) [Table 3; Fig. 2].Table 3 Serum concentrations of serotonin and kynurenine pathway metabolites and atopic dermatitis scales before and after blue light treatment

	Before the treatment	After 10 irradiations	p-value	
Median	Stand. dev	Median	Stand. dev	
Serotonin (mg/ml)	139.77	38.05	274.92	13.95	 < .00001*	
Quinolinic acid (mg/ml)	48.08	13.95	45.07	16.81	0.60942	
Kynurenic acid (mg/ml)	67.32	16.58	60.62	16.36	0.24883	
Tryptophan (mmol/l)	81.52	28.48	70.84	21	0.31383	
kynurenine (mmol/l)	3.32	1.56	3.1	1.5	0.98835	
EASI	13.16	3.59	8.65	2.06	0.00016*	
SCORAD	44.99	8.50	23.73	3.09	 < .00001*	
DLQI	14.37	7.65	7.42	5.65	0.00351*	
VAS	6.53	2.44	3.95	1.79	0.00251*	
10-Item Pruritus S.S	13.32	3.60	7.05	3.82	 < .00001*	
*Statistically significant						
EASI Eczema Area Severity Index, SCORAD SCORing Atopic Dermatitis, DLQI Dermatology Life Quality Index, VAS Visual Analogue Scale, 10-Item Pruritus S.S 10-item pruritus severity scale

Fig. 2 Full-body blue treatment in 20 patients with AD. EASI (13.16 vs. 8.65; p = 0.00016), SCORAD (44.99 vs. 23.73; p < 0.00001), DLQI (14.37 vs. 7.42; p = 0.0035), VAS (6.53 vs. 3.95; p = 0.00251), 10-item pruritus severity scale (13.32 vs. 7.05; p < 0.00001). AD Atopic dermatitis, EASI Eczema Area Severity Index, SCORAD SCORing Atopic Dermatitis, DLQI Dermatology Life Quality Index, VAS Visual Analogue Scale

Discussion

AD is a chronic disease that often occur in the general population. It has a significant impact on the quality of life of patient’s entire family. Among the treatment methods the topical, systemic and phototherapy are used, depending on the clinical severity. Blue light, as the UV-free method is a promising alternative due to its high safety profile. According to the currents studies it is believed to be safe with only few mild side effects reported. Termal discomfort, burning sensation, itching, local redness, local hyperpigmentation, dizziness, headache were reported only in a few patients and did not led to discontinuation of the therapy [10–15]. In this study we assessed the efficacy and safety of full-body blue irradiation in the treatment of moderate and severe atopic dermatitis. According to our findings we observed a significant change in EASI (13.16 vs. 8.65; p = 0.00016, improvement by 34.35%), SCORAD (44.99 vs. 23.73; p < 0.00001; improvement by 47.25%), VAS (6.53 vs. 3.95; p = 0.00251; improvement by 39.51%), 10-item pruritus severity scale (13.32 vs. 7.05; p < 0.00001; improvement by 47.11%) and DLQI (14.37 vs. 7.42; p = 0.00351; improvement by 48.36%) [Fig. 3; Fig. 4]. The EASI improvement was also observed in the previous clinical study using full body irradiation device (36 patients with AD, 2–3 cycles of 5 consecutive blue light-irradiations; wavelength > 66% of the spectrum 400–500 nm; 24 min of each body side exposure; 28.9 J/cm2; total fluence 43.7 J/cm2). In the study protocol patients were instructed to use topical corticosteroids 48 h after finishing blue light treatment cycle until complete skin lesion reduction. In case of a recurrence of the lesions, another cycle of irradiation was initiated. EASI was improved by 41% after 3 months and 54% after 6 months. Reduction of pruritus and improvement of sleep and life quality was also noted. Furthermore, another observation indicated a decrease in the frequency of disease relapses accompanied by milder symptoms and a reduced need for topical corticosteroid treatment. Moreover, the decrease in DLQI was observed after blue light therapy [12]. Several potential factors may account for better outcomes comparing to our study. Firstly, longer duration (48 vs 30 min) of individual irradiation session could have been significant. Moreover, the treatment was applied for patients with mainly severe AD (EASI of 20.6 ± 2.2 at the baseline, range 6.8–54). It is possible that patients with a severe course of the disease are likely to exhibit a greater degree of improvement compared to those with a milder course at the baseline, as it was observed in patients with psoriasis in the previous study [25]. Interestingly, in the recent randomized sham-controlled clinical trial in the arm treated with blue light 450 nm (25 patients, mean 21.1 irradiations over 8 weeks, 3 times per week) no significant changes in EASI, SCORAD, Investigator's Global Assessment (IGA) and DLQI scores were observed [13].Fig. 3 Before the treatment

Fig. 4 After 10 blue light irradiations

However, the improvement of ≥ 50% in EASI was observed in 24% patients in the 450 nm arm and mean SCORAD decreased, but not significantly comparing to the sham group. In that study after 450 nm irradiations significant reduction of pruritus in the Itch-VAS ((Itch-VAS, –1.6 ± 2.3; p = 0.023 vs. sham irradiation) was noted which was accompanied by decrease in IL-31 expression. The parameters of the device (450 nm wavelength, 40 mW/cm2, 36 J/cm2) were similar to the parameters used in our study, there was a minor variance in the wavelength used (450 nm vs 453 in our study). The possible hypothesis for observing greater improvement among patients in our study was higher disease severity of participants recruited to the study (median EASI 13.16, SCORAD 44.99 in our study vs EASI: 6.9 ± 8.0; SCORAD 37.3 ± 14.4 in Buhl et al. study). Another reason could be a more intense schedule of irradiations (3–5 times per week). Increasing the frequency of blue light irradiations may contribute to better treatment outcomes. A study comparing various treatment schedules (eg. 3 times per week vs 5 times per week vs daily application) would allow the development of the most effective protocol. Both studies indicate a positive effect of blue light on pruritus, which was also observed in our study [12, 13]. In the previous study the minimal clinically important difference was assessed and the moderate pruritus (3 to < 7) on VAS score at the baseline required a reduction of 1.34 points, which was observed in our study [26].

Additionally, of importance in our study is the involvement of pediatric population (7 patients, age 9–17). The treatment was well tolerated and effective. The inclusion criteria was the age above 8 years old. The age limit was set considering factors such as the child's ability to stay still during the irradiation procedure. To our knowledge this is the first study of blue light treatment involving patients under 18 years old. Further studies on larger cohorts of children are necessary to validate these findings.

Because there was a study which showed a potential impact of blue light on β-endorphin production, we decided to investigate if other substances related to mood regulation—serotonin and kynurenine pathway metabolites are also affected by blue light irradiation [23]. The serum concentrations of serotonin (mg/ml), quinolinic acid (mg/ml), kynurenic acid (mg/ml), tryptophan (mmol/l), and kynurenine (mmol/l) were examined in patients before and after 10 sessions of irradiation. Serotonin is a neurotransmitter associated with mood regulation, tryptophan is a precursor of serotonin [27]. Tryptophan can be converted into serotonin (serotonin pathway) or metabolized through kynurenine pathway. Kynurenine is a metabolite of tryptophan. Kynurenine pathway involves conversion of tryptophan into various metabolites including quinolinic acid and kynurenic acid. These metabolites have intricate functions in the central nervous system and are involved in mood-related conditions. Kynurenine pathway activation represents one of the mechanisms through which inflammation can trigger depression [28, 29]. Proinflammatory cytokines promote kynurenine pathway and consequently inhibit the activation of serotonin pathway of tryptophan, resulting in an overall reduction in serotonin synthesis [30]. Patients with AD, due to the chronic and recurrent nature of the disease along with the distressing itch, sleeplessness, are at risk of developing mood disorders and depression [31–34]. A treatment method that would also impact mood improvement would hold particular significance in a holistic approach to patient care. To our knowledge this is the first study assessing the impact of blue light on the concentration of serotonin and kynurenine pathway metabolites. 10 full body blue irradiations resulted in a statistically significant increase in the serum concentration of serotonin (139.77 mg/ml vs. 274.92 mg/ml); No other significant changes were observed in other serum parameters. However, an overall trend of downregulation of kynurenine pathway metabolites was observed.

In the literature it is noted that serotonin may be involved in the pathogenesis of AD [35, 36]. The recent study showed association between serotonergic markers and severity of the disease using the SCORAD scale [35]. In the study investigating the correlation between the serum concentration of serotonin and depression in adult patients with severe AD (31 patients with AD) it was found that severe AD correlates with depression and reduced serum serotonin levels (all patient with SCORAD > 50 had depression). The level of serotonin was significantly lover in patients with severe AD compare to a control group of 14 healthy individuals (85.7 ng/mL in the patients with AD with mild and moderate depression vs 294.9 ng/mL in healthy individuals). Moreover, adverse relation between the serotonin concentration and the depression severity was observed [37]. These finding may suggest that milder AD is correlated with higher serotonin concentration, which is consistent with our results. The possible hypothesis is that blue light irradiation leads to skin improvement, and milder AD is associated with higher serotonin levels. On the contrary, blue light could have an independent impact on enhancing mood. More studies are needed to better understand those associations.

There are limitations that should be taken into account when interpreting the findings of our study. First of all, the group of patients is relatively small, so the results need careful consideration. Secondly, another limitation of the study is the lack of a control group Additionally, the objective indices of atopic dermatitis were not evaluated. Conducting another study to assess the impact of blue light on parameters such as serum IgE, thymus and Activation-Regulated Chemokine (TARC), and eosinophil counts would be valuable. Developing a device that could be used at home might increase patients’ compliance, as some patients are reluctant to frequent phototherapy at the hospital or outpatient clinics. Lastly, the study did not assess long-term adverse effects. There is a need for conducting long-term patient observations to assess blue light safety profile.

Analyzing the impact of blue light on the serum concentration of serotonin and kynurenine pathway metabolites it should be considered whether the level of these metabolites in the serum correlates with the impact of these metabolites on brain concentration and brain function. There was one study limited to 27 patients which proved that changes in the serum levels of kynurenine correlated with cerebrospinal fluid levels [37]. Moreover, patients in our study were not assessed for depression.

Conclusion

In conclusion blue light seems to be a promising and safe treatment in patients with AD, but further investigations are needed to confirm those findings. Full body blue irradiations resulted in the improvement of sympthoms of AD, confirmed by objective methods of severity of the disease assessment as well as reduction of pruritus, an improvement of quality of life and an increase in blood serotonin levels. The use of this method should be considered in the treatment of other conditions associated with pruritus. Moreover, blue light could be a possible therapy for patients with contraindications to conventional therapies or as a combined therapy with conventional methods. There is a need to establish the optimal protocol for full body blue treatment and confirm its long-term safety.

Acknowledgements

We thank the participants of the study.

Author Contributions

Magdalena Sadowska, Joanna Narbutt, Daniel Nolberczak, Magdalena Ciążyńska, Małgorzata Skibińska, Dorota Sobolewska—Sztychny, David Aubert and Aleksandra Lesiak contributed to the study concept and design. All authors read and approved the final manuscript.

Funding

This research and the journal’s Rapid Service Fee were funded by statutory activities of Medical University of Lodz no. 503/1-064-01/503-11-001.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflict of Interest

Magdalena Sadowska, Joanna Narbutt, Daniel Nolberczak, Magdalena Ciążyńska, Małgorzata Skibińska, Dorota Sobolewska-Sztychny and Aleksandra Lesiak declare no conflict of interest. The research was conducted with co-operation with PHLECS B.V. (Eindhoven, Netherlands). David Aubert is the CEO of PHLECS B.V.

Ethical Approval

The study was approved by Ethics Committee of the Medical University of Lodz (RNN/223/20/KE 08.09.2020). Consent to participate and publish the data was obtained from all the participants. The patients agreed to the publication of their images. This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments.

Prior Presentation: The preliminary data were presented at the conferences: AAD Annual Meeting American Academy of Dermatology Association, Boston 25–29.03.2022r “The effectiveness and safety of blue light in the treatment of inflammatory skin diseases – the preliminary data”. SPIN—Skin Inflammation & Psoriasis International Network Congress 2022 The Fondation René Touraine, Paris 6–8.07.2022r “The effectiveness and safety of blue light in the treatment of atopic dermatitis and psoriasis vulgaris– the preliminary data”. ISAD International Society of Atopic Dermatitis, Gdansk, 31.08.23–2.09.2023 “Does blue light give happiness to the skin? Preliminary study in atopic dermatitis patients.”
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