System for irradiating a region of the skin of a subject

Abstract

The present invention relates to a system for irradiating a region of the skin of a subject with radiation covering the spectral area of 400 nm to 750 nm, the system comprising a radiation emitting unit, a radiation energy source, and a control unit. The system further comprises a subject interacting unit configured to interact with the subject to reduce a stress level of the subject and / or to improve the efficacy of the radiation emitted to the region of the skin of the subject. The present invention further relates to a system for use in the treatment of a subject suffering from chronic fatigue syndrome and / or an inflammatory skin disease.

Description

[0001] SYSTEM FOR IRRADIATING A REGION OF THE SKIN OF A SUBJECT

[0002] Field of the invention

[0003] The present invention relates to a system for irradiating a region of the skin of a subject. The present invention further relates to a system for use in the treatment of a subject suffering from chronic fatigue syndrome and / or an inflammatory skin disease.

[0004] System for irradiation

[0005] Background

[0006] Radiation-emitting devices for irradiating a region of the skin of a subject, such as devices used for (medical) phototherapy and devices used in cosmetics, e.g., hair removal devices, tanning devices, tattoo removal devices, are well-known in the art. Typically, devices for irradiating the skin of a subject are provided as radiation-emitting devices applied directly onto the skin of a subject, such as hand-held devices, for irradiating local areas of the skin or radiation-emitting devices located remote from the skin of a subject configured to irradiate a larger area of the skin of a subject, or even configured to perform a full-body irradiation of the skin of a subject. Irrespective the particular use of the device, i.e. , either to apply a phototherapy or irradiating the skin of a subject for wellness, cosmetic and / or aesthetic purposes, delivering of the irradiation dose to the subject in an effective, healthy and safe manner is a challenging process dependent on many factors.

[0007] For radiation-emitting devices applied directly onto the skin of a subject, providing the correct settings of radiation to irradiate the local area of the skin of the subject is less complex. Examples of such radiation-emitting devices are for example described in United States patent application US 2007 / 0208395 A1 , International patent application WO 2012 / 011013 A2, and United States patent application US 2017 / 0165498 A1. In such devices, due to the direct application of the device onto the skin, the complete delivery of the irradiation dose to the subject is safeguarded.

[0008] However, for radiation-emitting devices located remote from the skin of a subject for irradiating a larger area of the skin of the subject or even irradiating the full-body of the subject, providing the correct settings of radiation to irradiate the skin of the subject is much more complex and is not only dependent on the specifications of the device used, but also of the subject to be irradiated.

[0009] For example, in the field of phototherapy there are currently many phototherapy devices on the market emitting radiation at a defined wavelength that ranges from the ultraviolet to the Infra-Red, therefore including (visible) light (blue, green, yellow and red). An irradiation dose is delivered to the patient that is depending on the intensity of the radiance of the light source (in Joule) and the duration of the radiance. When the surface area of the skin is known, the power density of the irradiation of the skin can be calculated (W / cm2). The energy absorbed by the skin of the subject depends on the radiation dose emitted from the light device, the distance between the irradiated area and the radiation-emitting source, and the skin reflectance.

[0010] Given the complexity of irradiating the skin of a subject in a safe, healthy and effective manner, a reliable system for irradiating a region of the skin of a subject is described in International patent application WO 2023 / 239233 A1 providing for a system wherein the skin type of a subject to be irradiated is determined to take into account the skin reflectance of the subject.

[0011] Although the system as disclosed in International patent application WO 2023 / 239233 A1 provides for a reliable system, wherein the complete delivery of the irradiation dose to the subject is safeguarded, there is a constant need in developing methods and therapies for treating subjects with specific medical indications and / or treating subjects with higher efficacy.

[0012] Description of the invention

[0013] In a first aspect, the present invention provides hereto a system for irradiating a region of the skin of a subject with radiation covering the spectral area of 400 nm to 750 nm, wherein the system comprises: a radiation emitting unit configured to emit radiation covering the spectral area of 400 nm to 750 nm, wherein the radiation emitting unit is further configured to direct the radiation emitted to the region of the skin of the subject; a radiation energy source connected to the radiation emitting unit, wherein the radiation energy source is configured to supply an amount of energy to the radiation emitting unit; and a control unit communicatively connected to the radiation energy source and configured to control the supply of energy to the radiation emitting unit by controlling the radiation energy source.

[0014] The system of the present invention further comprises a subject interacting unit configured to interact with the subject to reduce a stress level of the subject and / or to improve the efficacy of the radiation emitted to the region of the skin of the subject.

[0015] It was found that by providing the system of the present, wherein irradiation of a region of the skin of a subject is combined with a subject interacting unit, such as a stress reducing element and / or radiation efficacy improving element, an improved phototherapy is provided resulting in an improved effect for the subject. It was found that by reducing the stress level of a subject simultaneously with or shortly before exposing the subject to the radiation emitted by the radiation emitting unit, the effect of the radiation emitted by the radiation emitting unit on the subject was significantly improved.

[0016] The system of the present may further comprise a measuring unit for measuring one or more physiological parameters of the subject, such as the temperature of the skin of the subject. To monitor, for example, the stress level of the subject, the measuring unit is preferably configured to measure stress-related physiological parameters. Such stress-related physiological parameters may be selected from the group consisting of heart rate, respiratory rate, body temperature, and blood pressure.

[0017] As used herein, the term “radiation emitting unit” refers to the radiation emitting part of a radiation emitting device, which device may be in the form of a hand-held device (to irradiate specific parts of the skin of a subject) or in the form of a radiation bed-like device, similar to an indoor tanning device, for providing a full body irradiation of the skin of a subject. The radiation emitting unit may be configured to comprise radiation emitting parts, like LEDs, OLED, fluorescent lamps or high-intensity discharge lamps. The radiation emitting parts may be configured to provide and select one or more wavelengths from a broad spectrum of wavelengths. Alternatively, the radiation emitting unit may be configured to provide various wavelengths using different radiation emitting parts, wherein each of the radiation emitting parts is able to provide a specific (narrow) range of wavelengths. The radiation emitting unit may also comprise one or more filters and / or an adjustable filter in order to select the required wavelength for irradiation of the skin of the subject. As used herein, the term “radiation energy source” refers to an energy source for providing energy to the radiation emitting unit. By adjusting the energy provided to the radiation emitting unit, the radiation intensity can be adjusted accordingly. Therefore, by controlling the radiation energy source of the system of the present invention, the radiation intensity of the radiation emitted from the radiation emitting unit can be controlled in a reliable and reproducible manner.

[0018] As used herein, the term “control unit” refers to a unit able to provide instructions to the radiation energy source. Optionally, the control unit of the system may be communicatively connected to the radiation emitting unit directly in order to select of define a relevant wavelength range for the irradiation of the skin of a subject. However, such direct communication is not necessary in case instructions are received from the user interface unit (e.g. a remote computer or smart device) communicatively connectable with the radiation emitting unit.

[0019] As used herein, the term “measuring unit” refers to a sensor unit able to measure one or more physiological parameters of the subject. The measuring unit may include many different sensors, wherein each sensor is able to monitor a specific physiological parameter. The measuring unit of the system of the present invention may also comprise a smart device, such as a smart watch worn by the subject to be irradiated, communicatively connectable with the system of the present invention, e.g. the control unit of the system of the present invention.

[0020] In general, the system comprising the radiation emitting unit, the radiation energy source, the control unit, and, optionally, the measuring unit, referred herein is typically a device for use in phototherapy. The system of the present invention thus combines a phototherapy device and a subject interacting unit, such as a stress reducing unit and / or radiation efficacy improving element in order to optimise the results of the phototherapy applied to a subject.

[0021] The subject interacting unit may be selected from a stress reducing unit, wherein the stress reducing unit is preferably a stress reducing unit configured to reduce a stress level of a subject by relaxation of the mind of the subject. Alternatively, or additionally, the stress reducing unit is a stress reducing unit configured to reduce a stress level of a subject by relaxation of the body of the subject.

[0022] Examples of stress reducing units that reduce stress by relaxation of the mind may include, but are not limited to, a virtual reality device and / or an audio device. The virtual reality device may be used to virtually locate the subject at a relaxing environment, such as typical scenery settings, including a sunny beach setting, a calming river setting, or a silent mountain setting. The audio device may be used to reduce stress promoting background noises and to introduce calming music.

[0023] Examples of stress reducing units that reduce stress by relaxation of the body may include, but are not limited to, a bath and / or a massage chair. Although any sort of bath may be used in the system of the present invention, a bath used in, for example, balneotherapy is preferred. It was observed that, physically, a bath used in, for example balneotherapy can induce temperature-related changes, like vasodilation and the release of endorphins.

[0024] Alternatively or additionally, the subject interacting unit may be selected from a radiation efficacy improving unit, wherein the radiation efficacy improving unit is preferably a radiation efficacy improving unit configured to improve the efficacy of the radiation emitted to the region of the skin of the subject, wherein the radiation efficacy improving unit is preferably configured to improve the skin characteristics of the subject. Examples of such a radiation efficacy improving unit may include, but are not limited to, a bath, a spray, a topical cream, and combinations thereof. Although any sort of bath may be used in the system of the present invention, a bath used in, for example, balneotherapy is preferred. By using a unit suitable for use in balneotherapy (also referred to as ‘balneotherapy unit’) water with salt and / or minerals is applied to the skin of the subject. It was observed that chemically, the minerals in the water can influence skin cell function and inflammation. The radiation emitting unit of the system of the present invention is preferably configured to emit radiation covering the spectral area of 400 nm to 500 nm, preferably covering the spectral area of 420 nm to 485 nm. Even further the radiation emitting unit of the system of the present invention is preferably configured to emit radiation covering the spectral area of 440 nm to 470 nm, preferably covering the spectral area of 450 nm to 460 nm.

[0025] In an embodiment of the present invention the system is configured to expose a region of the skin of a subject to violet, blue and / or cyan light. Preferably, the system of the present invention is configured to expose a region of the skin of a subject to blue light.

[0026] In a further embodiment of the present invention, the radiation emitting unit is configured to emit radiation covering the spectral area of visible light only. As used herein, the phrase ‘the radiation emitting unit is configured to emit radiation covering the spectral area of visible light only’ refers to a radiation emitting unit wherein radiation is emitted having wavelengths within the range of 400 nm to 750 nm. In other words, the phrase ‘the radiation emitting unit is configured to emit radiation covering the spectral area of visible light only’ refers to a radiation emitting unit wherein radiation is emitted not emitting wavelengths up to 400 nm and therefore excluding UV radiation and other harmful radiations, such as X rays and y rays.

[0027] In a second aspect, the present invention provides for a system according to the first aspect of the invention, for use in the treatment of a subject suffering from chronic fatigue syndrome and / or an inflammatory skin disease.

[0028] The chronic fatigue syndrome of the present invention may be selected from the group consisting of chronic fatigue syndrome associated with long COVID, Q fever fatigue syndrome, chronic fatigue syndrome associated with cancer or cancer therapies, post-traumatic stress disorder related chronic fatigue syndrome, and chronic fatigue syndrome associated with mental disorders including sleep disorder, depression and exhaustion disorder. Preferably, the chronic fatigue syndrome is chronic fatigue syndrome associated with long COVID.

[0029] As used herein, the term ‘chronic fatigue syndrome associated with cancer’ may refer to chronic fatigue syndrome associated with pancreas cancer, breast cancer, oral cavity cancer, and pharynx cancer.

[0030] As used herein, the term ‘chronic fatigue syndrome associated with cancer therapies’ may refer to chronic fatigue syndrome associated with chemotherapy, radiotherapy, surgery, immunotherapy, hormone therapy and combination therapies thereof.

[0031] The inflammatory skin disease may be selected from the group consisting of atopic dermatitis, herpes zoster, urticaria, psoriasis, eczema, pruritus, prurigo, vitiligo, rosacea, acne, Hidradenitis suppurativa, Govers disease, and ichthyosis.

[0032] Chronic fatigue syndrome

[0033] Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a complex multisystem disease commonly characterized by severe fatigue, cognitive dysfunction, sleep problems, autonomic dysfunction, and post-exertional malaise, which can severely impair patients’ ability to conduct the activities of daily living. Chronic fatigue syndrome affecting millions of people worldwide, whereas many clinicians lack the knowledge to appropriately diagnose or manage chronic fatigue syndrome. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful. Consequently, up to 91% of patients in the United States remain undiagnosed, and those diagnosed often receive inappropriate treatment. These problems are of increasing importance as recent developments show that, for example, after acute COVID-19, a significant percentage of people remain ill for many months with an illness similar to chronic fatigue syndrome.

[0034] There are many steps that clinicians can take to improve the health, function, and quality of life of those with chronic fatigue syndrome, including those in whom chronic fatigue syndrome develops after COVID-19. Patients with a lingering illness that follows acute COVID-19 who do not fully meet criteria for chronic fatigue syndrome may also benefit from these approaches. In addition to these approaches, there is a constant need of alternative methods to further improve the health, function, and quality of life of those with chronic fatigue syndrome.

[0035] Description of the invention

[0036] The present invention provides hereto a method of treating a subject suffering from chronic fatigue syndrome, wherein the subject is exposed to a phototherapy covering the spectral area of 380 nm to 500 nm. It was found that by exposing subjects suffering from chronic fatigue syndrome to the phototherapy of the present invention, a significant decrease in both Fatigue Severity Scale (FSS) and Short Form 36 Vitality Subscale (SF-36) was observed. The decrease in both FSS and SF-36 shows that exposure to the phototherapy of the present invention the subjective feeling of fatigue is reduced in subjects exposed to the phototherapy of the present invention.

[0037] In addition to the observed decrease in both FSS and SF-36, it was found that the phototherapy of the present invention results in a significant increase in tryptophan, kynurenine and serotonin, without changes in quinolinic acid and kynurenic acid serum levels after phototherapy. Without being bound by theory, the significant increase in tryptophan, kynurenine and serotonin, may implicate that the phototherapy of the present invention affects tryptophan metabolism and degradation pathway. The results may further implicate that the phototherapy of the present invention increases serotoninergic transduction and does not contribute to increase levels of tryptophan pathway metabolites associated with neurotoxicity (such as quinolinic acid).

[0038] The phototherapy according to the present invention may cover the spectral area of 400 nm to 490 nm, preferably may cover the spectral area of 420 nm to 480 nm. Even further the phototherapy according to the present invention may cover the spectral area of 440 nm to 470 nm, preferably may cover the spectral area of 450 nm to 460 nm.

[0039] The method of treating a subject suffering from chronic fatigue syndrome according to the present invention, may include a phototherapy wherein the subject is exposed to violet, blue and / or cyan light. Preferably, in the method of treatment according to the present invention, the subject is exposed to blue light.

[0040] The chronic fatigue syndrome treated by the phototherapy of the present invention may be selected from the group consisting of chronic fatigue syndrome associated with long COVID, Q fever fatigue syndrome, chronic fatigue syndrome associated with cancer or cancer therapies, post-traumatic stress disorder related chronic fatigue syndrome, and chronic fatigue syndrome associated with mental disorders including sleep disorder, depression and exhaustion disorder. Particular good results have been observed in a phototherapy for treating a subject suffering from chronic fatigue syndrome associated with long COVID.

[0041] As used herein, the term ‘chronic fatigue syndrome associated with cancer’ may refer to chronic fatigue syndrome associated with pancreas cancer, breast cancer, oral cavity cancer, and pharynx cancer.

[0042] As used herein, the term ‘chronic fatigue syndrome associated with cancer therapies’ may refer to chronic fatigue syndrome associated with chemotherapy, radiotherapy, surgery, immunotherapy, hormone therapy and combination therapies thereof.

[0043] Although the subject suffering from chronic fatigue syndrome may be exposed to the phototherapy of the present invention over various exposure times and dosage regimens, the subject suffering from chronic fatigue syndrome is preferably exposed to the phototherapy for about 5 to 30 minutes. Preferably the subject is exposed to the phototherapy for about 10 to 25 minutes, or further preferred to the phototherapy for about 15 to 20 minutes.

[0044] The phototherapy according to the present invention may be applied only once or, alternatively, multiple times a day. Preferably, the subject is exposed to the phototherapy over a period of time for a total of 5 to 20 treatments. For example, the subject may be exposed to the phototherapy of the present invention over a period of 2 to 4 weeks wherein the subject is exposed to the phototherapy with a minimum of 3 times a week.

[0045] Preferably, the subject is exposed to the phototherapy of the present invention once a day. Also, the phototherapy may be a single treatment therapy or a repeated treatment therapy. Such repeated treatment therapy is the preferred regimen, as particular good results are observed in subjects treated with the phototherapy of the present invention over a period of 10 days. As such, the subject suffering from chronic fatigue syndrome is preferably exposed to the phototherapy of the present invention once a day over a period of 8 days to 12 days, preferably over a period of about 10 days.

[0046] Experimental data

[0047] A study was conducted comprising 43 adults, 7 males (mean age 45.00±11.10), 36 females (mean age 38.00±12.82) who underwent COVID-19 infection confirmed by either RT-PCR or 2nd generation antigen test (material taken from nasopharyngeal swab). All participants were reporting subjective feeling of fatigue 4 weeks after resolution of the infection, which was confirmed by a board- certified physician. Other inclusion criteria: 18-65 years of age and lack of metabolic concomitant diseases (e.g., hypertension, hypothyroidism). Individuals with hypertension, photosensitivity-related conditions (e.g., porphyria, solar urticaria), active or cured skin cancers, taking immunosuppressive or photosensitizing drugs as well as pregnant and breastfeeding women were excluded from the study.

[0048] All participants underwent 10 full-body blue light irradiation using Phlecs Full Body Blue Gen 1.0 (Phlecs B.V., Eindhoven, Netherlands) emitting 453 nm light (irradiance 40 mW / cm2+ / - 3 mW / cm2) for 15 minutes a day in five consecutive days each week (2 days of pause). Before starting the study and after the full irradiation regimen all participants were assessed using the Fatigue Severity Scale (FSS), Short Form 36 Vitality Subscale (SF-36) and Dermatology Life Quality Index (DLQI). Additionally, serum samples were taken from 20 individuals to measure the levels of tryptophan, kynurenine, kynurenic acid, quinolinic acid and serotonin before and after irradiation.

[0049] The study showed that no significant changes in systolic blood pressure were noted (p=0.06), while diastolic blood pressure was significantly lower after 10 irradiations (from 81.2 to 78.5 mmHg, p=0.03) (data not shown). Considering clinical scales, a significant decrease in FSS (from 47.17±15.27 to 33.12±17.59, p<0.01), SF-36 (from 76.07±25.77 to 57.10±27.67, p<0.01) and DLQI (from 7.62±6.49 to 3.95±5.02, p<0.01) were observed. Detailed results are presented in Table 1 and Figure 1A (FSS), Figure 1 B (SF-36) and Figure 1C (DLQI).

[0050] Table 1. Changes in used clinical scales before and after irradiation.

[0051] Blue light irradiation also significantly increased the serum levels of tryptophan (from 66.77±21.24 to 71.24±21.27 mmol / l, p=0.03), kynurenine (from 2.58±1.15 to 3.10±1.51 mmol / l, p=0.02) and serotonin (from 240.55±81.19 to 274.93±99.66 ng / ml, p<0,01). Interestingly, the serum levels of quinolinic and kynurenic acid were unaffected by blue light therapy and no significant differences between study points has been revealed. Detailed results are shown in Table 2 and Figure 2A (tryptophan), Figure 2B (kynurenine) and Figure 2C (serotonin). A statistically significant moderate correlation was found between the kynurenic acid serum concentration and DLQI (Figure 3).

[0052] Table 2. Changes in kynurenine pathway serum levels before and after irradiation.

[0053] Balneophototherapy

[0054] Background

[0055] The beneficial effect of salt water baths and sun exposure (climatotherapy) on chronic skin diseases has been known for centuries. In many medical centres, especially in the Dead Sea area, remarkable results place climatotherapy on the list of the most effective treatment options for psoriasis and atopic dermatitis. As climatotherapy is tied to special geographical facts, balneophototherapies (also referred to as BPT) were alternatively established in German rehabilitation centres about 25 years ago. These balneophototherapies are used to treat chronic inflammatory skin diseases, and combine baths containing psoralens or salt with UVA or UVB radiation, respectively. The bath- and UV light-therapy can take place successively (asynchronous therapy) or simultaneously (synchronous therapy).

[0056] So far, there still does not exist a standardized treatment regimen of balneophototherapy. Natural spas (rehabilitation centres) or synthetic salt solutions of various concentrations (1% up to 30%) are used for balneophototherapy. The main ionic component is sodium chloride. In some treatment regimens (i.e., TOMESA® therapy) the amount of magnesium, calcium and sulphate are the same as in the Dead Sea water. The baths (temperatures typically in the range of 30°C to 35°C) are usually performed in pools (rehabilitation centres) or conventional bath-tubs for about 20 min. In order to reduce the volume of the saltwater, foil bath methods have been developed.

[0057] Generally, salt water baths are followed by artificial UV radiation; however, in TOMESA® therapy the baths and UV radiation are performed simultaneously in special tubs. Application of UV radiation in balneophototherapy corresponds to conventional phototherapy of psoriasis and atopic dermatitis.

[0058] Although balneophototherapy is a well-tolerated treatment modality severe heart and circulatory diseases are contraindications. A biting pain may occur in excoriated skin lesions especially bathing in water with high salt concentrations, and this must be taken into consideration in patients with atopic dermatitis. Hypersensitivity to salt water baths is a rare side-effect of balneophototherapy. Without doubt UV radiation is the predominant therapeutic factor in balneophototherapy. Nevertheless, additional effects can be addressed to bathing prior to phototherapy. Tap water and low concentration salt water baths increase permeability and water uptake by the stratum corneum. The water uptake is then followed by mineral uptake.

[0059] However, despite the above observations, it is noted that the heterogeneity of treatment regimens (different water composition, temperature, environment, and duration of therapy), small study sample sizes, and lack of blinded randomised controlled trials make it difficult to determine the true efficacy and benefit of balneophototherapies currently available. A well-studied but extreme example is the hypersaline Dead Sea, 400 m below sea level (climatotherapy). At this site there is less ultraviolet radiation, of which a greater proportion is UVA, than seen at sea level. This may enhance the value of exposure to natural sunlight while reducing the risk of sunburn.

[0060] In order to provide a more efficient and controllable balneophototherapy less prone to skin irritation, sunburn and exacerbation of photo dermatoses, an alternative balneotherapy treatment is needed.

[0061] Description of the invention

[0062] The present invention provides hereto a method of treating a subject suffering from an inflammatory skin disease, wherein the subject is exposed to a phototherapy treatment, simultaneously with or after a balneotherapy treatment. The present invention thus provides for a method of treating a subject suffering from an inflammatory skin disease, wherein the subject is exposed to a balneophototherapy. The balneophototherapy according to the present invention differs from the balneophototherapies known in the art in that the phototherapy treatment covers the spectral area of visible light only.

[0063] As used herein, the phrase ‘the phototherapy treatment covers the spectral area of visible light only’ refers to a phototherapy wherein radiation is used that is only emitting wavelengths within the range of 400 nm to 750 nm. As such, the present invention relates to a balneophototherapy wherein the subject is exposed to a phototherapy treatment, which phototherapy treatment covers the spectral area of 400 nm to 750 nm. In other words, the phrase ‘the phototherapy treatment covers the spectral area of visible light only’ refers to a phototherapy wherein radiation is used not emitting wavelengths up to 400 nm and therefore excluding UV radiation and other harmful radiations, such as X rays and y rays.

[0064] Given the balneophototherapy of the present invention, it was found that by providing the balneophototherapy for treating an inflammatory skin disease a significant reduction of itching was observed in the subject exposed to the treatment. But not only that, also a reduction of Eczema Area and Severity Index (EASI) was observed. In other words, the balneophototherapy of the present invention does not only lead to a balneophototherapy for treating a subject suffering from symptoms, such as itching, caused by an inflammatory skin disease, but the balneophototherapy of the present invention does also lead to a therapy wherein the underlying cause is treated, i.e., the inflammatory skin disease itself. In fact, studies showed a significant and tremendous reduction in EASI score after treating a subject suffering from an inflammatory skin disease with the balneophototherapy of the present invention.

[0065] In addition, besides observing a significant improvement in EASI score, by avoiding the use of a phototherapy that is primarily based on emitting radiation having a wavelength of up to 400 nm (e.g., emitting UV radiation), skin health and patient safety is further improved. Also, by avoiding exposing the subject to a phototherapy treatment that covers the spectral area of up to 400 nm, the subject may be treated for over a longer period of time with the phototherapy treatment, further enhancing the synergetic effect of combining the benefits of a balneotherapy treatment with the benefits of a phototherapy treatment. Finally, by providing a balneophototherapy lacking the use of a phototherapy treatment emitting wavelengths up to 400 nm, no special precautions or safety measures needs to be taken by the patient (except wearing protection glasses). Any patient, also patients highly sensitive to UV radiation can be treated with the balneophototherapy of the present invention.

[0066] The phototherapy treatment as used within the balneophototherapy for use according to the present invention preferably covers the spectral area of 400 nm to 500 nm, preferably covers the spectral area of 420 nm to 485 nm. The phototherapy treatment as used in the balneophototherapy of the present invention may cover the spectral area of 440 nm to 470 nm, preferably covers the spectral area of 450 nm to 460 nm. The inflammatory skin disease may be selected from the group consisting of atopic dermatitis, herpes zoster, urticaria, psoriasis, eczema, pruritus, prurigo, vitiligo, rosacea, acne, Hidradenitis suppurativa, Govers disease, and ichthyosis.

[0067] In an embodiment, the subject treated with the balneophototherapy of the present invention may be exposed to the balneotherapy treatment and may be simultaneously exposed to the phototherapy treatment. By combining both treatments and exposing the subject to both treatments at the same time, the highest synergistic effect of the advantages of both treatments is observed in patients.

[0068] However, in an alternative embodiment, the subject treated with the balneophototherapy of the present invention may be exposed to the balneotherapy treatment and may be subsequently, i.e., after finalizing the balneotherapy treatment, exposed to the phototherapy treatment. Although this successive method of treatment does not result in the highest synergistic effect of the advantages of both treatments, by providing such a successive method of treatment it is easier to expose the subject to the phototherapy in a highly efficient manner. In such way it might be easier to focus the phototherapy onto the subject skin area or areas to be treated without having negative interference from the balneotherapy treatment.

[0069] It is further noted that in case the subject is treating with the successive method of treatment, wherein the subject is first exposed to the balneotherapy treatment and subsequently exposed to the phototherapy treatment, the time period between both treatments is preferably as short as reasonably possible. Such time period between both treatments may be preferably less than 60 minutes, more preferably less than 30 minutes, even more preferably less than 20 minutes. In a preferred embodiment of the successive method of treatment, the subject is exposed to the phototherapy treatment within 10 minutes, preferably within 5 minutes, after finalizing the balneotherapy treatment.

[0070] Although the most preferred dosage regime is to apply the balneophototherapy once a day over a period of time (e.g., about 10 days), the subject may be exposed to multiple balneotherapy treatments and may be simultaneously exposed to the same number of multiple phototherapy treatments. Alternatively, the subject may be exposed to a balneotherapy treatment and may be subsequently exposed to multiple phototherapy treatments. As mentioned, in a preferred embodiment, the subject suffering from an inflammatory skin disease may be exposed to the balneophototherapy once a day. In addition, the subject suffering from an inflammatory skin disease may be exposed to the balneophototherapy over a period of 5 days to 16 days, preferably over a period of 8 days to 14 days, preferably over a period of 10 days to 12 days.

[0071] Also, the subject suffering from an inflammatory skin disease may be exposed to the balneophototherapy with a minimum of 3 times a week, preferably with a minimum of 5 times a week.

[0072] Although the subject suffering from an inflammatory skin disease may be exposed to the balneotherapy of the present invention over various exposure times and dosage regimens, the subject suffering from an inflammatory skin disease is preferably exposed to the balneophototherapy for about 1 hour, preferably for about 45 minutes, preferably for about 30 minutes, preferably for about 15 minutes.

[0073] Experimental data

[0074] A study was conducted including 10 adults (4 female and 6 male subjects) with a mean age of 49.40±20.28. The participants were exposed to a balneotherapy treatment and simultaneously exposed to a phototherapy treatment of 30 minutes once a day, for a period of 12 days (12 treatments in total). Before the start of the treatment cycle of 12 days and after finalizing the treatment cycle of 12 days, for each participant the EASI score was determined. Also, participants were asked to score their Pruritus Numerical Rating Scale (NRS) (Mean NRS and Worst NRS) before and after the treatment cycle of 12 days based on a scale of 0 (‘no itch’) to 10 (‘worst imaginable itch’). The results of the study are summarized in Table 3

[0075] Table 3. EASI scores and NRS before (B) and after (A) balneophototherapy treatment

[0076]

[0077] The results show a significant reduction in EASI score after 12 treatments (p<0.05), a significant reduction in Mean NRS (MNRS) after 12 treatments (p<0.05) and a significant reduction in Worst NRS (WNRS) after 12 treatments (p<0.05) was observed. The EASI score was reduced from 28.89±11.37 to 7.46±1.93. The Mean NRS was reduced from 7.20±1.89 to 0.90±0.07, and the Worst NRS was reduced from 8.10±1.76 to 1.20±1.25.

[0078] Another study was conducted including 50 adults. The participants were exposed to a balneotherapy treatment and simultaneously exposed to a phototherapy treatment once a day, for a period of 12 days (12 treatments in total). Before the start of the treatment cycle of 12 days and after finalizing the treatment cycle of 12 days, for each participant the ICD Pruritus (Itch Controlled Days questionnaire), the Eczema Area and Severity Index (EASI) score, and the SCORAD (SCOring Atopic Dermatitis) were determined. The results of the ICD Pruritus, the EASI score and the SCORAD are shown in, respectively, Figures 4A, 4B, and 4C. The results show that the combination treatment resulted in a significantly improved phototherapy treatment:

[0079] ICD Pruritus: 15.52 7.34 = -53%;

[0080] EASI score: 23.664 6.472 = -73%; and

[0081] SCORAD: 60.9 23.596 = -61 %.

Claims

CLAIMS1. System for irradiating a region of the skin of a subject with radiation covering the spectral area of 400 nm to 750 nm, the system comprising: a radiation emitting unit configured to emit radiation covering the spectral area of 400 nm to 750 nm, wherein the radiation emitting unit is further configured to direct the radiation emitted to the region of the skin of the subject; a radiation energy source connected to the radiation emitting unit, wherein the radiation energy source is configured to supply an amount of energy to the radiation emitting unit; and a control unit communicatively connected to the radiation energy source and configured to control the supply of energy to the radiation emitting unit by controlling the radiation energy source, characterised in that the system further comprises a subject interacting unit configured to interact with the subject to reduce a stress level of the subject and / or to improve the efficacy of the radiation emitted to the region of the skin of the subject.

2. System according to claim 1 , wherein the system further comprises a measuring unit for measuring one or more physiological parameters of the subject, such as the temperature of the skin of the subject.

3. System according to claim 2, wherein the measuring unit is configured to measure stress-related physiological parameters, such as stress-related physiological parameters selected from the group consisting of heart rate, respiratory rate, body temperature, and blood pressure.

4. System according to any of the preceding claims, wherein the subject interacting unit is a stress reducing unit configured to reduce a stress level of the subject: by relaxation of the mind of the subject; and / or by relaxation of the body of the subject.

5. System according to claim 4, wherein the stress reducing unit is selected from the group consisting of a virtual reality device, an audio device, a bath, a massage chair, and combinations thereof.

6. System according to any of claims 1-3, wherein the subject interacting unit is a radiation efficacy improving unit configured to improve the efficacy of the radiationemitted to the region of the skin of the subject, wherein the radiation efficacy improving unit is configured to improve the skin characteristics of the subject.

7. System according to claim 6, wherein the radiation efficacy improving unit is selected from the group consisting of a bath, a spray, a topical cream, and combinations thereof.

8. System according to claim 7, wherein the bath is a bath used in the balneotherapy.

9. System according to any of the preceding claims, wherein the radiation emitting unit is configured to emit radiation covering the spectral area of visible light only.

10. System according to any of the preceding claims for use in the treatment of a subject suffering from chronic fatigue syndrome and / or an inflammatory skin disease.

11. System according to any of claims 1-9 for use according to claim 10, wherein the chronic fatigue syndrome is selected from the group consisting of chronic fatigue syndrome associated with long COVID, Q fever fatigue syndrome, chronic fatigue syndrome associated with cancer or cancer therapies, post-traumatic stress disorder related chronic fatigue syndrome, and chronic fatigue syndrome associated with mental disorders including sleep disorder, depression and exhaustion disorder.

12. System according to any of claims 1-9 for use according to claim 11 , wherein the chronic fatigue syndrome associated with cancer is selected from the group consisting of chronic fatigue syndrome associated with pancreas cancer, breast cancer, oral cavity cancer, and pharynx cancer.

13. System according to any of claims 1-9 for use according to claim 11 , wherein the chronic fatigue syndrome associated with cancer therapies is selected form the group consisting of chronic fatigue syndrome associated with chemotherapy, radiotherapy, surgery, immunotherapy, hormone therapy and combination therapies thereof.

14. System according to any of claims 1-9 for use according to claim 10, wherein the inflammatory skin disease is selected from the group consisting of atopic dermatitis, herpes zoster, urticaria, psoriasis, eczema, pruritus, prurigo, vitiligo, rosacea, acne, Hidradenitis suppurativa, Covers disease, and ichthyosis.

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