Intranasal irradiation with the xenon chloride ultraviolet B laser

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                                       Journal of Photochemistry and Photobiology B: Biology xxx (2004) xxx–xxx

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

 4             Zsanett Csoma a, Ferenc Ignacz b, Zsolt Bor b, Gabor Szabo b, Laszlo Bodai a,
 5                                  Attila Dobozy a, Lajos Kemeny a,*
 6                            Department of Dermatology and Allergology, University of Szeged, P.O. Box 427, H-6701 Szeged, Hungary
 7                                 Department of Optics and Quantum Electronics, University of Szeged, H-6701 Szeged, Hungary
 8                                    Received 9 January 2004; received in revised form 23 April 2004; accepted 4 May 2004

 9 Available online

10 Abstract

11      We earlier reported that the 308 nm xenon chloride (XeCl) ultraviolet B (UVB) laser is highly effective for the treatment of
12   inflammatory skin diseases. Since UVB irradiation has been shown to exert both local and systemic immunosuppression, we in-
13   vestigated the clinical efficacy of UVB irradiation in allergic rhinitis. In an open study, groups of patients with severe allergic rhinitis
14   received intranasal irradiation with a 308 nm XeCl UVB excimer laser for two weeks. In the low-dose group ðn ¼ 10Þ, treatment was
15   given twice weekly, starting with 0.25 Â the individual minimal erythema dose (MED), whereas patients in the medium-dose group
16   ðn ¼ 8Þ were treated four times weekly, starting with 0.4 Â MED. In each group, the dosage was gradually increased. Evaluation was
17   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,
18   seven patients completed the study, and there was no improvement in the nasal symptoms. In the medium-dose group, the XeCl

19   UVB irradiation significantly inhibited the rhinorrhoea, the sneezing, the nasal obstruction and the total nasal score ðp < 0:05Þ. The
20   XeCl UVB excimer laser also inhibited the allergen-induced skin prick test in a dose-dependent manner. These results suggest that
21   the XeCl UVB excimer laser might serve as a new therapeutic tool in the treatment of allergic rhinitis.
22   Ó 2004 Published by Elsevier B.V.

23 Keywords: Ultraviolet B; Laser; Immunosuppression; Allergic rhinitis

24 1. Introduction                                                                     Allergic rhinitis is an inflammatory disorder of the               37
                                                                                   nasal mucosa characterized by nasal itch, sneezing,                   38
25      Allergic rhinitis is one of the most common health                         nose running and nasal blockage. The inflammation                      39
26   problems in many countries, because it is a high-cost,                        is a type I, or immediate hypersensitivity reaction of                40

27   high-prevalence disease, affecting about 15–30% of the                         the nasal mucosa that arises in consequence of an                     41
28   population [1]. The number of the patients with allergic                      allergen-immunoglobulin E (IgE) interaction in senz-                  42
29   rhinitis is still increasing, especially in the well-devel-                   itized individuals. For the treatment of the disease,                 43
30   oped, industrialized countries. Although it is not asso-                      well-established pharmacological therapies with anti-                 44
31   ciated with severe morbidity and mortality, allergic                          histamines, corticosteroids, decongestants and mast                   45
32   rhinitis has a major effect on the quality of life. Its                        cell stabilizers are available. New therapeutic options               46

33   increasing prevalence, its impact on the individual                           have recently become increasingly important, includ-                  47
34   quality of life and social costs [2,3] and its role as a risk                 ing leukotriene modifiers, anti-IgE antibodies, phos-                  48
35   factor for asthma [4], underline the need for improved                        phodiesterase inhibitors and intranasal heparin, and                  49
36   treatment options for this disorder.                                          there have been developments in appropriate allergen-                 50
                                                                                   specific immunotherapy [5]. However, complete                          51
                                                                                   suppression of the clinical symptoms cannot be                        52
           Corresponding author. Tel.: +36-62-545-252; fax: +36-62-545-954.        achieved in most cases with the currently available                   53
           E-mail address: (L. Kemeny).                 drugs.                                                                54

     1011-1344/$ - see front matter Ó 2004 Published by Elsevier B.V.
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 55      Ultraviolet (UV) light has been shown to exert both               previous four weeks, topical corticosteroids or cromolyn         107
 56   local and systemic immunosuppression [6–10], and has                 sodium within two weeks, antihistamines and decon-               108
 57   been widely used for decades in the therapy of various               gestants within one week prior to the beginning of the           109
 58   skin diseases. The major mechanisms of UV irradiation-               study or immunotherapy in the past two years. The                110
 59   induced immunosuppression involve apoptosis induc-                   patients were enrolled into two groups, and an open-             111
 60   tion in infiltrating T cells, reductions in the number of             label study was performed to assess the tolerability and         112

 61   Langerhans cells and function, and the induction of                  the efficacy of the XeCl excimer laser in allergic rhinitis.       113
 62   immunosuppressive cytokines such as interleukin-10 in                The investigation was performed between 15 August                114
 63   the skin [8,11–14]. The results of many studies have                 and 20 September 2001, and the ragweed pollen counts             115
 64   confirmed that both broad-band UVB (wavelength 280–                   were above 50/m3 in Szeged area throughout the study.            116
 65   320 nm), narrow-band UVB (310–313 nm), ultraviolet A                 Informed consent according to the Institutional Review           117

 66   (UVA; 315–400 nm), combined UVA–UVB and high-                                                         o
                                                                           Board of the Albert Szent–Gy€rgyi Medical Center at              118
 67   dose UVA1 (340–400 nm) inhibit histamine release from                the University of Szeged, was obtained from each indi-           119
 68   mast cells in vitro and in vivo [15–19]. For UVB treat-              vidual before the start of the study.                            120
 69   ment, a promising new therapeutic modality is the
 70   ‘‘super narrow-band’’ 308 nm xenon chloride (XeCl)                   2.1.2. Low-dose XeCl laser treatment group                       121
 71   excimer laser, which has been found to be more effective                 The patients in group 1 ðn ¼ 10Þ received low-dose            122

 72   than narrow-band UVB in inducing T cell apoptosis in                 XeCl laser irradiation. The light source was a 308 nm            123
 73   vitro and is also clinically more effective for the treat-            XeCl excimer laser (Lambda Physics LPX 105 E). The               124
 74   ment of an inflammatory skin disease, psoriasis [20–22].              energy density of each light impulse was 15.11 mJ/cm2            125
 75      Although the different atopic diseases, e.g. atopic                with a duration of 15 ns, with a laser repetition rate of        126
 76   dermatitis and allergic rhinitis, share many common                  10 Hz. The minimal erythema dose (MED) of each pa-               127
 77   pathogenetic factors, and there are a large number of                tient was determined first by irradiating the skin in the         128
 78   phototherapeutic modalities for the treatment of atopic              gluteal region with different dosages (100–600 mJ/cm2 )           129
 79   dermatitis, the use of UV-based therapies for the treat-             of the XeCl laser. The MED values were read off 24 h              130
 80   ment of allergic rhinitis has never been reported.                   after the irradiation. The treatment of the nasal mucosa         131
 81   Therefore, we were interested in whether such photo-                 was performed by means of a special instrument for               132
 82   therapy might also be effective for the treatment of al-              targeted phototherapy (Rhinolight handpiece, Rhino-              133
 83   lergic rhinitis. We describe here that the XeCl excimer              light, Hungary), and started with a fluence of 0.25 Â the         134
 84   laser is effective in suppressing the skin prick test reac-           individual MED. The handpiece of the instrument was              135
 85   tion and the clinical symptoms of patients with hay                  introduced into the nasal cavity of the patients, and its        136
 86   fever. These results suggest that intranasal phototherapy            distal end was carefully moved continuously in order to          137
 87   might serve as a new tool in the anti-allergic arsenal for           be able to irradiate homogenously large area of the nasal        138
 88   the treatment of allergic rhinitis.                                  mucosa (Fig. 1). Two treatments were given weekly for            139
                                                                           two weeks. After the first treatment, the dosage of the           140
                                                                           UV light was increased in steps of 0.125 Â MED up to             141

 89 2. Methods                                                             0.625 Â MED. The patients scored the severity of their           142
                                                                           clinical symptoms (sneezing, nasal itching, nose running,        143
 90 2.1. Assessment of tolerability and efficacy of intranasal               nasal blockage) on a four-point scale once a day in a            144
 91 XeCl laser therapy in hay fever

 92   2.1.1. Patients

 93      Fifteen patients (f:m ¼ 11:4, age between 18 and 65
 94   years, mean: 44.6 years) were examined; all suffered
 95   from severe, ragweed-induced hay fever, that did not
 96   respond well to conventional antiallergic treatment, all
 97   had a history of rhinitis of at least two ragweed seasons,
 98   and the diagnosis was confirmed by positive skin prick

 99   test results to ragweed (a wheal greater than 5 mm) and
100   by measurement of the ragweed-specific IgE antibody
101   level. Patients with significant nasal structural abnor-
102   malities, bronchial asthma, an upper respiratory tract
103   infection within the past two weeks or a lower respira-
104   tory infection within four weeks prior to the start of the
105   study were excluded. Further exclusion criteria were
106   treatment with systemic corticosteroids within the                          Fig. 1. Instrument used for the intranasal irradiation.
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145   diary; 0 ¼ no symptoms, 1 ¼ mild, 2 ¼ moderate and                   were then examined with this antigen on the irradiated             197
146   3 ¼ severe symptoms. The total nasal score (TNS) was                 and non-irradiated control skin areas 24 and 48 h after            198
147   calculated as the sum of the severity scores. All side               irradiation.                                                       199
148   effects observed during the treatment were recorded. In
149   the course of the study, the patients did not use any                2.3. Statistical analysis                                          200
150   antiallergic drugs.

                                                                              The effects of intranasal XeCl laser irradiation on the          201
151   2.1.3. Medium-dose XeCl laser treatment group                        clinical symptoms were analysed by the Wilcoxon’s Sum              202
152      The patients in group 2 ðn ¼ 8Þ received medium                   of Ranks test, comparing the clinical scores at the be-            203
153   dose XeCl laser irradiation. The treatment of the                    ginning with those at the end of the treatment period. To          204
154   nasal mucosa started with a fluence of 0.4 Â MED,                     evaluate the effect of XeCl laser irradiation on the de-            205

155   increased in steps of 0.125 Â MED or to the individual               velopment of allergen-induced wheals, the size of the              206
156   tolerance level. Four treatments were given weekly for               wheals that developed on the irradiated areas were                 207
157   two weeks. The patients scored the severity of their                 compared with those on the non-irradiated control test             208
158   clinical symptoms in the same way as in group 1.                     areas. Differences in wheal size were analysed statisti-            209
159   Again, all side effects were recorded during the                      cally by means of the two-tailed, matched Student’s                210
160   treatment.                                                           t-test. A probability level p < 0:05 was considered to be          211

                                                                           a statistically significant difference.                              212
161 2.2. Effect of XeCl laser irradiation on the immediate
162 hypersensitivity reaction in the skin
                                                                           3. Results                                                         213
163   2.2.1. Patients
164      Patients with a history of allergic rhinitis (n ¼ 7, f:m
                                                                           3.1. Effects of the low-dose XeCl laser treatment on the            214
165   ¼ 5:2, mean age: 21.85 years) were enrolled in this
                                                                           clinical symptoms of allergic rhinitis                             215
166   study. Patients discontinued taking antihistamines and
167   corticosteroids two weeks prior to the performance of
                                                                              Of the 10 enrolled patients, seven completed the two-           216
168   the skin prick test. Informed consent was obtained from
                                                                           week treatment period. Three patients dropped out be-              217
169   each individual before the study. The individual MED
                                                                           fore completing the study, because of the significant               218
170   was determined by irradiating the skin in the gluteal
                                                                           worsening of their symptoms (lack of effect). Following             219
171   region with increasing doses of XeCl excimer laser
                                                                           treatment, there was no significant improvement in the              220

172   (Lambda Physics LPX 105 E). After the MED mea-
                                                                           sneezing, rhinorrhoea, nasal itching, nasal blockage or            221
173   surements 4 cm2 test areas on the volar forearm of each
                                                                           TNS (Fig. 2). The patients tolerated the treatment well,           222
174   patient were irradiated with the XeCl laser, in dosages of
                                                                           and no severe side effects were observed. Mild dryness of           223
175   0.5 Â MED, 1.0 Â MED and 2.0 Â MED. Twenty-four
                                                                           the nasal mucosa occurred in two patients; this did not            224
176   and 48 h after the irradiation, skin prick tests were
                                                                           need any intervention, and it disappeared within few               225
177   performed with the same antigen on both the irradiated

                                                                           days after the last treatment.                                     226
178   and non-irradiated skin areas.

179   2.2.2. Skin prick test                                               3.2. Effects of the medium-dose XeCl laser treatment on             227
180      The skin prick test is a method that is widely used               the clinical symptoms of allergic rhinitis                         228
181   to investigate the immediate hypersensitivity reaction
182   to a specific allergen in the skin [23]. Skin prick tests                All eight patients enrolled in the medium-dose XeCl             229

183   were performed with recombinant allergens (Soluprick-                laser group completed the study. After the two-week                230
184   Epipharm Allergie-Service GmbH). Ragweed, muggle,                    treatment period, significant improvements were ob-                 231
185   cat and dog hair antigens were used for the investi-                 served in the sneezing, rhinorrhoea, and nasal blockage            232
186   gations. Twenty-microlitre aliquots of the test solu-                scores and also in the TNS (Fig. 3). The improved                  233
187   tions were placed on the patients’ forearms, with a                  clinical symptoms were usually first noted four to five              234
188   distance of more than 3 cm between individual appli-                 days after the start of therapy, and thereafter the im-            235

189   cation points. Sterile 0.9% sodium chloride solution                 provement was continuous. At the end of the XeCl laser             236
190   and histamine hydrochloride were used for control                    treatment, the symptom scores were reduced by more                 237
191   purposes. Reactions were recorded 20 min after testing               than 50%. The XeCl laser treatment also reduced the                238
192   and the wheal size was measured by digital planimetry.               severity of nasal itching, but the decrease was statisti-          239
193   After determination of the individual sensitivity of                 cally not significant. No severe side effects occurred, but          240
194   each patient, for each individual one allergen was                   mild dryness of the nasal cavity was observed in six of            241
195   chosen that induced an ‘‘optimal’’ wheal of approxi-                 the eight patients; this was relieved by application of a          242
196   mately 10 mm in diameter. Skin prick test reactions                  vitamin A-containing oil.                                          243
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      Fig. 2. Changes in the individual clinical symptoms and TNS during the low-dose UVB treatment. No significant change was found (Wilcoxon’s Sum
      of Ranks Test, n ¼ 7) in the nasal scores during the two-week treatment period.

244 3.3. Effects of XeCl laser irradiation on the immediate                     on histamine-induced wheal formation (data not                         262
245 hypersensitivity reaction in the skin                                      shown).                                                                263

246      The XeCl excimer laser induced a dose-dependent
247   inhibition of the allergen-induced wheal formation                       4. Discussion                                                          264

248   (Fig. 4). When the skin prick test was performed 24 h
249   after the XeCl laser irradiation, the size of the wheal                     In the present study we found that intranasal UVB                   265
250   induced by the allergen decreased by 7.8% at                             phototherapy with medium-dose 308 nm XeCl excimer                      266
251   0.5 Â MED, by 35.2% at 1 Â MED and by 55.3% at                           laser significantly suppressed the nasal symptoms of                    267
252   2 Â MED, as compared with that on the non-irradiated,                    patients with severe hay fever, whereas in low dosages                 268
253   control side. The inhibition was statistically significant                had no effect on the symptoms. The XeCl UVB excimer                     269

254   at dosages of 1 Â MED and 2 Â MED (p < 0:05, Student                     laser also inhibited the allergen-induced skin prick test              270
255   t-test). When the skin prick test was performed 48 h                     reaction in a dose-dependent manner, suggesting that                   271
256   after XeCl laser treatment, the inhibition of wheal for-                 excimer laser inhibits allergen-induced histamine release              272
257   mation was less than that obtained 24 h after treatment,                 from the mast cells.                                                   273
258   but the difference was still significant. On the 2 Â MED                      UV irradiation has been successfully used for the                   274
259   laser irradiation, the wheal size was approximately 40%                  treatment of hyperproliferative and inflammatory skin                   275
260   less than the size of the wheal on the non-irradiated                    diseases for many years. Initially, broad-band UV light                276
261   control areas. The XeCl laser irradiation had no effect                   sources in the UVB range 290–320 nm were used for                      277
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      Fig. 3. Improvement in the individual clinical symptoms and TNS during the medium-dose UVB treatment. The clinical scores of sneezing, rhin-
      orrhoea, nasal blockage and the TNS decreased significantly (p ¼ 0:018, 0.035 and 0.013, respectively; Wilcoxon’s Sum of Ranks Test, n ¼ 8) during
      the two-week treatment period.

278   such treatment, but during the last few years these light                      To assess the efficacy of phototherapy in hay fever,                   296
279   sources have been replaced with the more efficient nar-                      we used the biologically most effective UVB light source,                 297
280   row-band UVB light sources operating at 310–313 nm                         the 308 nm XeCl excimer laser. For the treatment of                      298
281   [7]. We recently introduced new, highly effective XeCl                      skin diseases with narrow-band UVB irradiation, the                      299

282   excimer laser-based UVB phototherapy for the treat-                        therapy is started usually with a UVB dose of                            300
283   ment of different skin diseases [21,22,24,25]. The XeCl                     0.8 Â MED dose, which is gradually increased, depend-                    301
284   laser was found to be more effective than conventional                      ing on the patient’s tolerance, and irradiation is per-                  302
285   UVB light sources in the phototherapy of skin disorders                    formed three to four times weekly [7]. Since the XeCl                    303
286   [20,22]. These results have been confirmed by other                         excimer laser is more effective than narrow-band UVB,                     304
287   groups and the 308 nm excimer laser is currently widely                    and since there were no data on the tolerability of the                  305

288   used for the treatment of skin diseases [26,27]. We have                   nasal mucosa to the XeCl excimer laser, we started the                   306
289   further recently demonstrated that the XeCl excimer                        treatment of the nasal cavity with a lower UVB dosage                    307
290   laser is highly effective for the treatment of an atopic                    than that we usually apply in the therapy of skin dis-                   308
291   disease, atopic dermatitis (manuscript in preparation).                    eases. It emerged that the intranasal XeCl excimer laser                 309
292   As there are many common pathogenetic factors in                           illumination had no effect on the clinical symptoms of                    310
293   atopic dermatitis and allergic rhinitis, we have now ad-                   patients with hay fever when the treatment was started                   311
294   dressed the question of whether phototherapy might                         at the low dosage of 0.25 Â MED twice weekly, but a                      312
295   also be effective for the treatment of hay fever.                           significant improvement was seen when the treatment                       313
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                                                                                   cells, and much has also been learned as regards how            346
                                                                                   UVB phototherapy affects the inflammatory cells in the            347
                                                                                   skin. UVB irradiation results in a reduction in the             348
                                                                                   number of epidermal Langerhans cell [6], increases the          349
                                                                                   production of immunosuppressive cytokines in macro-             350
                                                                                   phages [13,29–31], induces apoptosis in the T cells [20],       351

                                                                                   in activated mast cells [30] and eosinophils (manuscript        352
                                                                                   in preparation), inhibits histamine release from the mast       353
                                                                                   cells in vitro [15,16]; all of these effects might account for   354
                                                                                   the observed clinical efficacy of UVB irradiation in al-          355
                                                                                   lergic rhinitis.                                                356

                                                                                       To determine whether the XeCl laser also had an             357
                                                                                   effect on the allergen-induced histamine release from            358
                                                                                   mast cells, we investigated the effects of XeCl laser ir-        359
                                                                                   radiation on the skin prick test reaction. In the skin          360
      Fig. 4. UVB irradiation suppresses the allergen-induced wheal size.          prick test, the antigen induces a rapid release of hista-       361
      Values represent wheal size 24 and 48 h (light and dark bars, respec-
                                                                                   mine from the sensitized mast cells and results in the          362
      tively) after irradiation with different doses of UVB expressed as a

      percentage of the untreated control. Error bars represent the standard       development of a wheal in 10–20 min. We found that the          363
      error of mean. *: p < 0:05, the statistical significance of the results was   XeCl laser significantly suppressed allergen-induced             364
      evaluated by using the two-tailed, matched Student’s t-test ðn ¼ 7Þ.         wheal development, suggesting that the UVB irradiation          365
      Significant decreases were observed 24 h after irradiation at 1 Â MED         directly targets the mast cells in the skin, too. The fact      366
      and 2 Â MED (p ¼ 0:048 and 0.029, respectively) and 48 h after ir-
                                                                                   that the XeCl laser had no effect on histamine-induced           367
      radiation at 2 Â MED ðp ¼ 0:034Þ.
                                                                                   wheal formation suggests that the XeCl laser inhibits           368
                                                                                   histamine release from the mast cells. Our data are in          369
314   was started with 0.4 Â MED and was continued with                            good accord with other findings suggesting that UV ir-           370
315   increasing dosages four times weekly. Mild dryness of                        radiation significantly reduced the size of the allergen         371
316   the nasal mucosa was the only side effect observed, but it                    induced wheal in the skin prick test [17–19]. Whole-body        372
317   disappeared completely within a few days after the last                      UVB irradiation, excluding the prick test areas, did not        373
318   XeCl laser treatment.                                                        significantly influence the wheal and flare responses to           374
319      The mechanism of action of the XeCl excimer laser in                      common aeroallergens, suggesting that the UVB-irra-             375
320   allergic rhinitis might involve many different factors that                   diation induced inhibition of histamine release is a local      376
321   play a role in the pathogenesis of the disease. In allergic                  effect of the UVB light [19]. Fjellner et al. demonstrated       377
322   rhinitis, the initial response to the allergen involves the                  that moderate doses of UVB irradiation inhibited the            378
323   activation of immune cells. The allergen is presented by                     histamine-release effect of compound 48/80 from rat              379
324   Langerhans cells and the allergen-specific IgE is gener-                      peritoneal mast cells in vitro, while higher doses of UVB       380
325   ated by the B cells under the regulation of T cells. The                     light caused cytotoxic histamine leakage from the mast          381

326   IgE molecules produced bind to IgE receptors (FceRI                          cells [32]. UVB irradiation was also capable of inhibiting      382
327   and FceRII) present on the surface of mast cells, mac-                       compound 48/80-induced mast cell degranulation in               383
328   rophages and eosinophils (sensitization phase). After                        both mice and humans [33,34]. All these results suggest         384
329   repeated exposure to the allergen, it binds and activates                    that the inhibition of histamine release from mast cells        385
330   the cells sensitized with IgE. As a result of this activa-                   by UVB irradiation is probably mediated by a direct             386
331   tion, histamine and other preformed mediators are re-                        membrane stabilization effect.                                   387

332   leased from the mast cells and different inflammatory                              Similarly as for topical corticosteroids used for the       388
333   mediators and cytokines are produced locally in the                          treatment of the disease, UV light by its immunosup-            389
334   immune cells. These mediators and cytokines activate                         pressive effect might facilitate the appearance of viral         390
335   the structural cells and are responsible for the recruit-                    and bacterial infections on the treated areas. However,         391
336   ment of eosinophils and basophils from the circulation                       we did not observe any infections during this study; the        392
337   (effector phase). The increased number of activated im-                       only side effect was mild dryness of the treated areas.          393

338   mune cells then display a greater immune response to                             It is well known that repeated irradiation with UV          394
339   the next exposure to the allergen resulting in more severe                   light in high doses has a carcinogenic potential. This          395
340   clinical symptoms [28]. Although we do not have direct                       depends on the cumulative dose (usually requiring many          396
341   data, as to how UVB influences these processes in the                         years), and the irradiation doses applied for the photo-        397
342   nasal mucosa, mainly the mechanisms of the effector                           therapy of the nasal mucous membranes are much lower            398
343   phase could be influenced by UVB irradiation, because                         than dose leading to an increased risk of cancer; the risk      399
344   patients were already sensitized. There are numerous in                      of carcinogenesis with the present therapeutical schemes        400
345   vitro data on the effects of phototherapy on immune                           is therefore thought to be very low.                            401
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402      Neuman and Finkelstein used 660-nm narrow-band,                       [2] A.W. Law, S.D. Reed, J.S. Sundy, K.A. Schulman, Direct costs of         450
403   low-energy, red-light phototherapy for treatment of the                      allergic rhinitis in the United States: estimates from the 1996         451
404   nasal mucosa by inserting a red-light-emitting photodi-                      Medical Expenditure Panel Survey, J. Allergy Clin. Immunol. 111         452
                                                                                   (2003) 296–300.                                                         453
405   ode into the nasal cavity [35]. They found that their red-               [3] D.A. Stempel, R. Woolf, The cost of treating allergic rhinitis,         454
406   light therapy was effective for the treatment of perennial                    Curr. Allergy Asthma Rep. 2 (2002) 223–230.                             455
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408   action of red light might involve stimulation of antiox-                     integration, J. Allergy Clin. Immunol. 111 (2003) 1171–1183.            457
409   idant enzymes, and thereby the suppression of oxygen                     [5] A. Schultz, B.A. Stuck, M. Feuring, K. Hormann, M. Wehling,             458
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410   radicals formed in the allergic reaction. By inducing a                      Allergy Clin. Immunol. 3 (2003) 21–27.                                  460
411   profound immunosuppression, phototherapy with the                        [6] M.S. Duthie, I. Kimber, R.J. Dearman, M. Norval, Differential            461
412   XeCl excimer laser differs completely from that with                          effects of UVA1 and UVB radiation on Langerhans cell migration           462

413   low-intensity red light. Furthermore, in addition to its                     in mice, J. Photochem. Photobiol. B: Biol. 57 (2002) 123–131.           463
414   well-characterized immunosuppressive effect, UV irra-                     [7] A.A. El-Ghorr, M. Norval, Biological effects of narrow-band (311         464
                                                                                   nm TL01) UVB irradiation: a review, J. Photochem. Photobiol. B:         465
415   diation has been shown to be able to induce antigen-                         Biol. 38 (1997) 99–106.                                                 466
416   dependent specific tolerance to a given antigen in mice                   [8] J. Krutmann, Therapeutic photoimmunology: photoimmunolog-               467
417   [36]. Whether a similar antigen-dependent specific tol-                       ical mechanisms in photo(chemo)therapy, J. Photochem. Photo-            468
418   erance might be induced in patients with allergic rhinitis                   biol. B: Biol. 44 (1998) 159–164.                                       469
                                                                               [9] B.J. Vermeer, M. Hurks, The clinical relevance of immunosup-            470

419   by irradiation of the nasal mucosa with UVB light
                                                                                   pression by UV irradiation, J. Photochem. Photobiol.B: Biol. 24         471
420   during exposure to the allergen is not known.                                (1994) 149–154.                                                         472
421      The present study has revealed that UVB photo-                       [10] H.M. Salo, E.I. Jokinen, S.E. Markkula, T.M. Aaltonen, H.T.             473
422   therapy with the XeCl excimer laser is effective for the                      Penttila, Comparative effects of UVA and UVB irradiation on the          474
423   treatment of hay fever. As UV irradiation has not only a                     immune system of fish, J. Photochem. Photobiol. B: Biol. 56              475
424   profound immunosuppressive effect, but also a signifi-                         (2000) 154–162.                                                         476
                                                                              [11] K. Kalimo, L. Koulu, C.T. Jansen, Effect of a single UVB or PUVA         477
425   cant antiproliferative effect, UV-based phototherapies                        exposure on immediate and delayed skin hypersensitivity reactions       478
426   might be effective for the treatment of nasal polyps, too.                    in humans. Correlation to erythemal response and Langerhans cell        479
427   These data suggest that phototherapy is of a promise as                      depletion, Arch. Dermatol. Res. 275 (1983) 374–378.                     480
428   a new method for the treatment of allergic rhinitis, but                [12] J. Garssen, R.J. Vandebriel, F.R. De Gruijl, D.A. Wolvers, M.           481
429   further studies are necessary to establish which wave-                       Van Dijk, A. Fluitman, H. Van Loveren, UVB exposure-induced             482
                                                                                   systemic modulation of Th1- and Th2- mediated immune                    483
430   lengths are therapeutically most effective and safe for the                   responses, Immunology 97 (1999) 506–514.                                484
431   treatment of inflammatory and hyperproliferative dis-                    [13] D.X. Nghiem, N. Kazimi, D.L. Mitchell, A.A. Vink, H.N.                  485

432   orders of the nasal mucosa.                                                  Ananthaswamy, M.L. Kripke, S.E. Ullrich, Mechanisms under-              486
                                                                                   lying the suppression of established immune responses by ultra-         487
                                                                                   violet radiation, J. Invest. Dermatol. 119 (2002) 600–608.              488
433 5. Abbreviations                                                          [14] J. Garssen, H. Van Loveren, Effects of ultraviolet exposure on the       489
                                                                                   immune system, Crit. Rev. Immunol. 21 (2001) 359–397.                   490
434   IgE    Immunoglobulin E                                                 [15] K. Danno, K. Fujii, T. Tachibana, K. Toda, T. Horio, Suppressed         491
                                                                                   histamine release from rat peritoneal mast cells by ultraviolet B       492

435   MED    minimum erythema dose                                                 irradiation: decreased diacylglycerol formation as a possible           493
436   TNS    total nasal score                                                     mechanism, J. Invest. Dermatol. 90 (1988) 806–809.                      494
437   UV     ultraviolet                                                      [16] C. Kronauer, B. Eberlein-Konig, J. Ring, H. Behrendt, Influence of       495
438   UVB    ultraviolet B                                                         UVB, UVA and UVA1 irradiation on histamine release from                 496
439   XeCl   xenon chloride                                                        human basophils and mast cells in vitro in the presence and absence     497
                                                                                   of antioxidants, Photochem. Photobiol. 77 (2003) 531–534.               498
                                                                              [17] K. Kalimo, L. Koulu, C.T. Jansen, Effect of a single UVB or PUVA         499

440 Acknowledgements                                                               exposure on immediate and delayed skin hypersensitivity reactions       500
                                                                                   in humans. Correlation to erythemal response and Langerhans cell        501
                                                                                   depletion, Arch. Dermatol. Res. 275 (1983) 374–378.                     502
441      We thank Prof. Dr. Annika Scheynius (Department                      [18] R. Gollhausen, K. Kaidbey, N. Schechter, UV suppression of              503
442   of Medicine, Unit of Clinical Allergy Research, Karo-                        mast cell-mediated wealing in human skin, Photodermatol. 2              504
443   linska Institute, Stockholm, Sweden) for careful reading                     (1985) 58–67.                                                           505
444   of the manuscript and for her suggestions for improve-                  [19] E. Vocks, K. Stander, J. Rakoski, J. Ring, Suppression of               506

                                                                                   immediate-type hypersensitivity elicitation in the skin prick test by   507
445   ment. This study was supported by the NKFP 1A/0012,                          ultraviolet B irradiation, Photodermatol. Photoimmunol. Pho-            508
446   OMFB 01620 and ETT 419/2003 grants.                                          tomed. 15 (1999) 236–240.                                               509
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                                                                                   Dobozy, L. Kemeny, Xenon chloride ultraviolet B laser is more           511
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