Innovation in the treatment of non-melanoma skin cancer: daylight photodynamic therapy / Új eljárás a nem melanoma típusú bordaganatok kezelésében: "daylight" fotodinámiás terápia

Introduction: Photodynamic therapy is indicated for the treatment of superficial basal cell carcinoma, Bowen's disease and actinic keratosis. Reactive oxygen radicals are released from the metabolite of the topically applied photosensitizer that is excited by light, which selectively leads to the destruction of tumor cells. The procedure can be performed with an artificial light source or with the use of sunlight. The latter is called daylight photodynamic therapy, which is an effective and painless procedure. Objective: Our aim was to introduce daylight photodynamic therapy in actinic keratoses at our department and to optimize the treatment protocol for the local climatic conditions. Method: Three clinical trials were performed. The difference between the treatment protocols was between the incubation time of the photosensitizer on the skin and in the time patients spent under the sunlight. Results: When using the international treatment protocol, 73% of the actinic keratoses showed complete, while 27% partial remission. By reducing the proportion of time patients spent outdoor, complete remission was achieved in

Open, prospective, multicenter study on postoperative intranasal phototherapy in nasal polyposis.

BACKGROUND: The therapeutic effect of ultraviolet (UV) light is generally attributed to its immunosuppressive and immunomodulatory effects. Since chronic inflammation is the major factor in the development of nasal polyposis, we have previously used mixed ultraviolet-visible light (mUV-VIS, Rhinolight®) phototherapy for the treatment of nasal polyps. AIMS: In the present open, multicenter study, our aim was to delineate whether mUV-VIS applied postoperatively in vivo together with intranasal steroid treatment could reduce the recurrence of nasal polyps. METHODS: After functional endoscopic sinus surgery, one group of patients received mUV-VIS light together with standard intranasal steroid (mometason furoate 2 × 200 µg) application for a 12-week treatment period, whereas the other patient group obtained only intranasal steroid for the same duration. We recorded nasal endoscopy images and obtained demographical and clinical data, total nasal score (TNS), and nasal obstruction symptom evaluation (NOSE). We performed acoustic rhinometry and measured nasal inspiratory peak flow. Follow-up was 12 months. RESULTS: We found that the recurrence of nasal polyps was significantly diminished, and based on video-endoscopic measurements, the size and grade of recurrent polyps were significantly smaller in the phototherapy-receiving group. Nasal obstruction values and NOSE were significantly better throughout the follow-up period in the mUV-VIS light-treated group than in the intranasal steroid monotreatment group. CONCLUSIONS: Rhinophototherapy together with standard nasal steroid application may have a supportive role in the treatment of recurrent bilateral nasal polyps.

Phototherapy-induced blistering reaction and eruptive melanocytic nevi in a child with transient neonatal porphyrinemia.

Neonatal blue-light phototherapy induced a blistering reaction followed by eruption of melanocytic nevi on the exposed skin surface of a child with transient neonatal porphyrinemia. New nevi are still developing 4 years after the triggering event. The role of phototoxicity-induced epidermal injury, that of porphyrins and the influence of neonatal blue-light therapy, in this unique phenomenon are discussed.

Ultraviolet light and photodynamic therapy induce apoptosis in nasal polyps.

Intranasal phototherapy has been found to be effective for the treatment of nasal polyposis (NP) therefore the aim was to investigate the apoptosis inducing effect of phototherapy in NP. In this ex vivo study nasal polyp tissue was surgically collected from 21 consecutive patients with chronic rhinosinusitis (CRS) associated with NP. The removed polyps were cut into pieces and tissue samples were irradiated in vitro by different doses of combined ultraviolet and visible light (UV/VIS: 280-650 nm) and by selective ultraviolet and visible light (sUV/VIS: 295-650 nm). Photodynamic therapy (PDT) was performed by presensitizing tissue samples with 5-delta-aminolevulinic acid (DALA) then irradiated with visible light (VIS: 395-650 nm). Tunel assay was applied to detect apoptosis of epithelial and inflammatory cells in irradiated and control nasal polyp tissue samples. UV/VIS light significantly increased epithelial cell and subepithelial leukocyte apoptosis compared to control groups. PDT treatment showed the highest surface epithelial cell as well as subepithelial leukocyte apoptosis compared to all other groups. Intranasal phototherapy may serve as a new potential therapeutical method in treatment of NP.

PUVA treatment of the nasal cavity improves the clinical symptoms of allergic rhinitis and inhibits the immediate-type hypersensitivity reaction in the skin.

We earlier reported that intranasal irradiation with the 308 nm xenon chloride (XeCl) ultraviolet-B laser and irradiation with a combination of ultraviolet-B (UVB), ultraviolet-A (UVA) and visible light (VIS) is highly effective in the treatment of allergic rhinitis and inhibit the immediate-type hypersensitivity reaction in the skin. Since photochemotherapy with 8-methoxypsoralen (8-MOP) plus UVA light (PUVA) is widely used in the treatment of different inflammatory skin disorders due to its immunosuppressive effect, in the present study we investigated the efficacy of intranasal PUVA treatment in allergic rhinitis and the effect of PUVA treatment on the skin prick test (SPT) reaction. An open study was performed in 17 patients with hay fever. Intranasal PUVA therapy was given four times weekly for 3 weeks. The treatment was started with a fluence of 0.5x of the individual minimal phototoxic dose (MPD) and the dosages were gradually increased. Evaluation was based on the symptom scores. The effect of PUVA treatment on the allergen-induced wheal formation was also studied in the SPT. PUVA treatment of the nasal cavity significantly decreased the nasal symptoms of the patients with allergic rhinitis. Treatment of the skin with PUVA also significantly suppressed the allergen-induced wheal formation in the SPT reaction. These data suggest that intranasal PUVA phototherapy is also an effective modality in the treatment of allergic rhinitis.

[Intranasal phototherapy for the treatment of allergic rhinitis]. / Intranasalis fototerápia az allergiãs rhinitis kezelésében.

INTRODUCTION: Allergic rhinitis is a frequent disease, accompanied by significant social-economic costs and a negative impact on the quality of life. Phototherapy has a profound immunosuppressive effect and is effectively used in the treatment of several immune mediated skin diseases such as atopic dermatitis. AIMS: The authors investigated the efficacy of intranasal phototherapy with a combination of low doses of ultraviolet-B, ultraviolet-A and visible light in allergic rhinitis. METHODS: A randomized, double-blind, placebo-controlled study was conducted in patients with a history of at least 2 years of moderate to severe ragweed-induced allergic rhinitis that was not controlled by anti-allergic drugs. Intranasal phototherapy was performed 3 times a week for 3 weeks. As placebo low intensity visible light was used. RESULTS: Phototherapy resulted in a significant improvement of clinical symptoms for nasal itching, rhinorrhea, sneezing and total nasal score. Scores for nasal obstruction slightly improved during phototherapy while a significant increased was found in the placebo group. In the overall efficacy assessment, both patients and investigators found phototherapy significantly more efficient than placebo. Phototherapy was well tolerated, the only side effect was the slight dryness of the nasal mucosa. CONCLUSIONS: These results suggest that intranasal phototherapy is effective for the treatment of allergic rhinitis, and opens up new opportunities for the treatment of immune-mediated mucosal diseases.

Rhinophototherapy: a new therapeutic tool for the management of allergic rhinitis.

BACKGROUND: Phototherapy has a profound immunosuppressive effect and is able to inhibit hypersensibility reactions in the skin. OBJECTIVE: We evaluated whether phototherapy using a combination of UV-B (5%), UV-A (25%), and visible light (70%), referred to as mUV/VIS, is effective in treating allergic rhinitis. METHODS: We conducted a randomized, double-blind study, in 49 patients with hay fever. The study was performed during the ragweed season. Each intranasal cavity was illuminated 3 times a week for 3 weeks with mUV/VIS or with low-intensity visible light. Symptom scores, inflammatory cells, and their mediators were assessed in nasal lavages. In vitro effects of mUV/VIS irradiation on T-cell and eosinophil apoptosis and its inhibitory effect on mediator release from basophils were examined. RESULTS: Rhinophototherapy was tolerated well and resulted in a significant improvement of clinical symptoms for sneezing (P < .016), rhinorrhea (P < .007), nasal itching (P < .014), and total nasal score (P < .004). None of the scores improved significantly in the control group. Scores for nasal obstruction slightly improved after mUV/VIS treatment and significantly increased in the control group (P < .017). In the nasal lavage, phototherapy significantly reduced the number of eosinophils and the level of eosinophil cationic protein and IL-5. In vitro irradiation of T cells and eosinophils with mUV/VIS light dose-dependently induced apoptosis. Furthermore, mUV/VIS irradiation inhibited the mediator release from RBL-2H3 basophils. CONCLUSION: These results suggest that phototherapy is an effective modality to treat allergic rhinitis and offer new options for the treatment of immune-mediated mucosal diseases.

Inhibition of immediate type hypersensitivity reaction by combined irradiation with ultraviolet and visible light.

Recently we found that ultraviolet B (UVB) irradiation in erythematous doses significantly inhibited the immediate type hypersensibility reaction in the skin. In the present study we investigated the effects of different wavelengths on the skin prick test reaction (SPT). The forearm of ragweed allergic patients was irradiated with increasing doses of ultraviolet A (UVA), visible light (VIS) or combined UVB, UVA and VIS light, referred to as mUV/VIS. SPTs were performed 24 h after irradiation both on irradiated and non-irradiated control skin areas using ragweed extract. UVA and VIS irradiation led to a slight, not significant inhibition of allergen-induced wheal formation. Mixed irradiation with mUV/VIS light resulted in a dose-dependent inhibition of the allergen-induced wheal formation. The inhibition was significant already at suberythematous doses. As there is a good correlation between SPT and the nasal symptoms in patients with hay fever these data suggest that phototherapy with mUV/VIS light might be an effective and safe treatment modality for immediate type hypersensibility reactions in the skin and nasal mucosa.

Intranasal irradiation with the xenon chloride ultraviolet B laser improves allergic rhinitis.

We earlier reported that the 308 nm xenon chloride (XeCl) ultraviolet B (UVB) laser is highly effective for the treatment of inflammatory skin diseases. Since UVB irradiation has been shown to exert both local and systemic immunosuppression, we investigated the clinical efficacy of UVB irradiation in allergic rhinitis. In an open study, groups of patients with severe allergic rhinitis received intranasal irradiation with a 308 nm XeCl UVB excimer laser for two weeks. In the low-dose group (n=10), treatment was given twice weekly, starting with 0.25x the individual minimal erythema dose (MED), whereas patients in the medium-dose group (n=8) were treated four times weekly, starting with 0.4x MED. In each group, the dosage was gradually increased. Evaluation was based on the symptom scores. The effect of the XeCl laser on the skin prick test reaction was also studied. In the low-dose group, seven patients completed the study, and there was no improvement in the nasal symptoms. In the medium-dose group, the XeCl UVB irradiation significantly inhibited the rhinorrhoea, the sneezing, the nasal obstruction and the total nasal score (p<0.05). The XeCl UVB excimer laser also inhibited the allergen-induced skin prick test in a dose-dependent manner. These results suggest that the XeCl UVB excimer laser might serve as a new therapeutic tool in the treatment of allergic rhinitis.

Xenon chloride ultraviolet B laser is more effective in treating psoriasis and in inducing T cell apoptosis than narrow-band ultraviolet B.

Earlier we reported that a 308-nm xenon chloride (XeCl) UVB laser is highly effective for treating psoriasis. As ultraviolet B light seems to cause T cell apoptosis, in the present study we studied the ability of the XeCl laser to induce T-cell apoptosis in vitro, and then compared the apoptosis-inducing capacities of narrow-band UVB (NB-UVB) light and the XeCl laser. The role of laser impulse frequency and intensity in the therapeutical and apoptosis-inducing efficacy of XeCl laser was also investigated. Both XeCl laser and NB-UVB induced T cell apoptosis, but quantitative induction was greater with XeCl laser. Changes in the frequency and intensity of impulses of XeCl laser did not influence its therapeutic and T cell apoptosis-inducing efficacy. These results suggest that the more effective induction of T cell apoptosis can be responsible for the greater clinical efficacy of XeCl laser compared to NB-UVB. Additionally, the optical properties of the XeCl laser (a monochromatic, coherent, pulse-mode laser; easier precise dosimetry, there are no 'contaminating' wavelengths) can make this laser light an ideal tool for studies of the mode of action of UVB light.