摘要
目的：观察311nm窄谱中波紫外线(NB-UVB)与280nm～320nm宽谱中波紫外线(BB-UVB)治疗寻常型银屑病的临床疗效及对比分析比较，为临床广泛应用和选择窄谱中波紫外线治疗银屑病提供科学客观的临床研究依据。
材料和方法：用自身双侧对比照射NB-UVB和BB-UVB方法治疗寻常型银屑病52例，分别在治疗前和治疗后1，2，3，4周对患者皮损的红斑、鳞屑、浸润进行临床观察，并以银屑病严重程度ESI评分标准评分，分析其皮损清除率和治愈率，以spss11.5软件包分析统计学结果。
结果：50例可评价患者治疗前ESI评分为15.95±6.32分，经NB-UVB照射后，患者在4周内每周ESI评分分别为10.32±5.43，6.85±6.41，3.13±2.52，1.27±2.36；皮损清除率分别为(35.43±8.62)％，(59.5±10.57)％，(82.29±15.03)％和(90.42±9.97)％，治愈人数分别为1，18，26，42人，治愈率为2％，36％，52％，88％。而经BB-UVB照射后，患者每周ESI评分分别为12.36±6.58，9.57±55.32，5.14±3.68，3.08±3.75；皮损清除率平均分别为(31.02±12.50)％，(51.27±13.67)％，(73.34±20.38)％和(83.86±8.59)％，治愈人数分别为0，9，15，35人，治愈率为0，18％，30％，70％。两组患者治疗1周和治疗前相比，NB-UVB治疗组ESI评分有显著降低(p＜0.05)，BB-UVB治疗组ESI评分无显著改善(p＞0.05)；治疗2、3、4周与治疗1周后相比，两组患者ESI评分、皮损清除率和治愈率均有显著性差异(p＜0.05)，且随治疗时间的延长，ESI评分有显著性降低(p＜0.05)，皮损清除率和治愈率均有显著性增加(p＜0.05)。治疗1周后，NB-UVB组ESI评分显著低于BB-UVB组(p＜0.05)，皮损清除率显著高于BB-UVB组(p＜0.05)，而两组间治愈率无显著性差异(p＞0.05)；治疗2、3、4周后，NB-UVB组ESI评分显著低于BB-UVB组(p＜0.05)，而皮损清除率和治愈率显著高于BB-UVB组(p＜0.05)。
结论：NB-UVB治疗寻常型银屑病治疗时间短，治愈率高，其临床疗效明显优于BB-UVB。
目的：研究311nm窄谱中波紫外线(NB-UVB)与280nm～320nm宽谱中波紫外线(BB-UVB)对寻常型银屑病患者血清可溶性TNF-α1受体(sTNF-R1)、IFN-γ和IL-4水平的影响及311nm NB-UVB对皮损中IFN-γ和IL-4表达的影响，并结合其临床疗效，来探讨其治疗的部分机制。材料与方法：60例寻常型银屑病患者随机分为NB-UVB，BB-UVB，对照3组，每组20例，每周光疗3次，共4周，对照组不予光疗。治疗前后分别以银屑病严重程度PASI评分标准评分，以ELISA法测定血清中sTNF-R1、IFN-γ和IL-4水平，以免疫组化方法和图像分析系统分析IFN-γ和IL-4在NB-UVB和对照组银屑病皮损中的表达，结果以积分光密度值(IOD值)表示，并与10例正常人比较，结果应用spss11.5软件包进行统计学处理。
结果：临床疗效：3组患者治疗前PASI评分分别为18.58±11.12，17.13±10.50，18.93±11.42，无显著性差异(p＞0.05)；治疗后评分均下降，分别为2.65±1.36，5.32±3.28，9.99±7.27，NB-UVB组分别低于BB-UVB和对照组(p＜0.05)。血清学水平：sTNF-R1：疗前3组血清sTNF-R1水平为2.064±0.33 ng／ml，2.11±0.35 ng／ml，2.10±0.31 ng／ml，较正常人1.47±0.21ng／ml为高(p＜0.05)，治疗后3组sTNF-R1水平分别为1.57±0.33 ng／ml，1.78±0.22 ng／ml，1.92±0.17 ng／ml(p＜0.05)，NB-UVB组最低(p＜0.05)。IFN-γ：3组治疗前IFN-γ为34.16±5.50 pg／ml，34.21±7.92 pg／ml，34.21±6.25pg／ml，均较正常人5.46±1.04 pg／ml为高(p＜0.05)；治疗后为12.46±1.46pg／ml，23.81±2.54 pg／ml，27.74±1.73 pg／ml，均较治疗前降低(p＜0.05)，NB-UVB组分别低于BB-UVB组和对照组(p＜0.05)。IL-4：治疗前3组血清IL-4水平为6.19±2.39 pg／ml，6.45±3.42 pg／ml，6.78±3.12 pg／ml，与正常人5.75±2.26 pg／ml无明显差异(p＞0.05)，治疗后IL-4水平无明显变化(p＞0.05)，分别为5.63±1.93 pg／ml，5.55±1.58 pg／ml，6.71±4.04 pg／ml。免疫组织化学和图像分析结果：IFN-γ：NB-UVB和对照组2组患者皮损IFN-γ表达均较正常人增高(p＜0.05)，IOD值分别为(28.163±6.501)×10~2，(28.892±4.251)×10~2，(6.174±2.012)×10~2；治疗后2组患者IOD值下降(p＜0.05)，为(7.021±1.892)×10~2，(15.74±2.733)×10~2，NB-UVB组低于对照组(p＜0.05)。IL-4：疗前2组患者IOD值为(4.991±4.257)×10~2，(4.253±2.849)×10~2；治疗后2患者组IL-4表达增高(p＜0.05)，为(15.762±2.325)×10~2，(10.754±3.573)×10~2，NB-UVB组高于对照组(p＜0.05)。
结论：NB-UVB对改善寻常型银屑病临床症状方面优于BB-UVB，对血清sTNF-R1、IFN-γ的影响方面强于BB-UVB。NB-UVB可以同时调节寻常型银屑病血清IFN-γ水平和皮损中IFN-γ，IL-4的表达，通过改善患者体内Th1，Th2失衡状态而达到治疗效果。
Objective: To observe and to analyze the clinical efficacy of 311nm narrowband UVB (NB-UVB) and 280～320nm broadband UVB (BB-UVB) phototherapy in patients with psoriasis vulgaris, so as to provide an objective basis for selecting NB-UVB to treat psoriasis.
Methods: A total of 52 patients with psoriasis vulgaris were treated with 311nm NB-UVB radiation at one side of body and 280～320nm UVB radiation at the other side of body. Erythema, scale, and induration were chosen as the observative parameters before and after the 1st, 2nd, 3rd, and the 4th week treatment. The efficacy was evaluated by ESI score to analyze the remission rates of lesions and cure rates, and spss 11.5 software was used for statistical analysis.
Results: ESI scores of 50 patients involved were assessed before the treatment and 1, 2, 3, and 4 weeks after the treatment. Pre-treatment ESI scores were 15.95±6.32. After NB-UVB radiation, in the 1st, 2~(nd), 3rd and 4th week, ESI scores were 10.32±5.43, 6.85±6.41, 3.13±2.52 and 1.27±2.36, remission rates of lesions by NB-UVB were (35.43±8.62) %, (59.5±10.57)%, (82.29±15.03) % and (90.42±9.97) %, and the numbers of patient clear were 1, 18, 26,42 and clear rates were 2%, 36%, 52%, 88% respectively. In contrast, after radiation of BB-UVB, in 1~(st),2nd,3~(rd) and 4th week, ESI scores were 12.36±6.58, 9.57±55.32, 5.14±3.68 and 3.08±3.75, remission rates of lesions were (31.02±12.50) %, (51.27±13.67) %, (73.34±20.38) % and (83.86±8.59) %, and the numbers of patient clear were 0, 9, 15, 35 and clear rates were 0, 18%, 30%, 70% respectively. After 1 week of treatment, ESI scores of NB-UVB group decreased significantly(p＜0.05), while which of BB-UVB group had no significant difference (p＞0.05) .In the 2~(nd),3~(rd) and 4th week, compared with the 1st week, ESI scores, remission rates of lesions and cure rates in both groups had significant difference(p＜0.05),and with the duration of treatment, remission rates of lesions and clear rates increased and ESI scores decreased significantly. After 1 week of treatment, ESI scores of NB-UVB group decreased more significantly than which of BB-UVB group (p＜0.05), remission rates of lesions increased more significantly than which of BB-UVB group(p＜0.05), and between NB-UVB and BB-UVB group, there was no significant difference of clear rates (p＞0.05 ). After 2,3,4 weeks of treatment, ESI scores of NB-UVB group decreased more significantly than which of BB-UVB group (p＜0.05), and remission rates of lesions and clear rates of NB-UVB group compared with which of BB-UVB group increased more significantly(p＜0.05).
Conclusion: Compared to BB-UVB, NB-UVB takes shorter time and has higher cure rate, it is superior to BB-UVB in term of treatment of psoriasis vulgaris.
Objective: This study was designed to observe the effects of 311nm NB-UVB and 280nm～320nm BB-UVB on the serumal soluble TNF-R1 receptor 1 (sTNF-R1), IFN-γand IL-4 in the patients with psoriasis vulgaris, and to investigate the level of IFN-γand IL-4 in lesions of patients treated with 311nm NB-UVB, so as to explore its possible theraputic mechanism with the clinical efficacy..
Method: 60 cases with psoriasis vulgaris were divided into 3 groups randomly, NB-UVB group, BB-UVB group, and control group. Each group included 20 patients was given phototherapy 3 times per week, and 4 weeks of treatment totally, and control group was not given any phototherapy. The severity of psoriasis was evaluated by PASI score, and serumal sTNF-R1, IFN-γand IL-4 were detected by ELISA before and after treatment, and the expression of IFN-γand IL-4 in skin lesions were analyzed by immunohistochemistry and image-analysis system before and after treatment.All the results were shown as IOD, and compared with the normal value.and then analyzed statistically by spss 11.5 software. significantly to 2.65±1.36, 5.32±3.28, 9.99±7.27 respectively in 3 groups, and which of NB-UVB group was the lowest (p＜0.05).Serum results:sTNF-R1: The levels of serumal sTNF-R1 of 3 groups were 2.06±0.33 ng/ml, 2.11±0.35 ng/ml, 2.10±0.31 ng/ml respectively, all of which were higher than that in normal volunteer's serum(1.47±0.21 ng/ml) before treatment(p＜0.05),and decreased significantly after treatment to 1.57±0.33 ng/ml, 1.78±0.22 ng/ml, 1.92±0.17 ng/ml respectively (p＜0.05). The level of serumal TNF-R1 in NB-UVB group decreased more significantly than that in BB-UVB group and in control group (p＜0.05).IFN-γ: The levels of serumal IFN-γof 3 groups were34.16±5.50 pg/ml, 34.21±7.92 pg/ml, 34.21±6.25 pg/ml respectively, all of which were higher than normal volunteers'(5.46±1.04 pg/ml) (p＜0.05) , and decreased significantly to 12.46±1.46 pg/ml, 23.81±2.54 pg/ml, 27.74±1.73 pg/ml respectively after treatment(p＜0.05). The level of IFN-γ, of NB-UVB group decreased more significantly than that of BB-UVB group and control group (p＜0.05). IL-4: The levels of serumal IL-4 in 3 groups were 6.19±2.39 pg/ml, 6.45±3.42 pg/ml, 6.78±3.12 pg/ml respectively, and showed no significant difference among the study groups and normal volunteers'(5.75±2.26 pg/ml) before treatment (p＞0.05) .After treatment, the levels of IL-4 of the 3 study groups were 5.63±1.93 pg/ml, 5.55±1.58 pg/ml, 6.71±4.04 pg/ml respectively and no significant change existed (p＞0.05) . Immunohistochemistry and image-analysis results: IFN-γ: The level of IFN-γin lesions increased before treatment in both NB-UVB and control groups compared to normal skin(p＜0.05), and IOD were (28.163±6.501)×10~2, (28.892±4.251)×10~2 , (6.174±2.012)×10 respectively, and decreased significantly to (7.021±1.892)×10~2 , (7.021±1.892)×10~2 after treatment(p＜0.05), and which of NB-UVB group decreased more significantly than that of control group(p＜0.05).IL-4: The IOD of IL-4 were (5.263±3.204)×10~2, (4.991±4.257)×10~2 , (4.253±2.849)×10~2 respectively before treatment, and which had no significant difference with the normal group. After treatment, the IOD of IL-4increased to ( 15.762±2.325 )×10~2 , (10.754±3.573)×10~2 (p＜0.05), and which increased more significantly in NB-UVB group than that in control group(p＜0.05).
Conclusion- NB-UVB is superior to BB-UVB in improvement of PASI score and decrease of serumal sTNF-R1, IFN-γin term of the treatment of psoriasis vulgaris. At the same time, NB-UVB has a therapeutic effect on psoriasis vulgaris by regulating the level of IFN-γin serum and IFN-γ,IL-4 in lesions to improve the imbalance of Thl and Th2.
引文
1. Tjioe M, Smits T, van de Kerkhof PC, et al. The differential effect of broad band vs narrow band UVB with respect to photodamage and cutaneous inflammation [J]. Exp Dermatol. 2003,12(6):729-733.
2. Todd RC, Lauren H.B, Patricia Gilleaudeau R.N, et al. Narrowband UV-B produces superior clinical and histopathological resolution of moderate-to-severe psoriasis in patients compared with broadband UV-B[J]. Arch Dermatol. 1997, 133 (12): 1514-1522.
3. Lebwohl M, Christophers E, LangleyR, et al. Aninternational, randomized, double-blind, placebo-controlled phase 3 trial of intramuscular alefacept in patients with chronic plaque psoriasis.[J].Arch Dermatol. 2003,139(6):719-727.
4. Leanutaphong V, Sudtims A. A comparision of erythema efficacy of ultraviolet B irradiation from Philips TL 12 and TL 01 lamps [J]. Photochematol Photoimunol Photomed. 1998, 14: 112-115.
5. Gibbs NK, Traynor NJ, Mackie RM, et al. The phototumorigenic potential of broad-band (270-350nm) and narrow-band (311-313nm) phtotherapy sources can not be predicted by their edematogenic potential in hairless mouse skin[J]. J Invest Dermatol. 1995, 104:359-363.
6. Hansen A B, Bech-Thomsen N, Walf H C. Erythema after irradiation with ultraviolet B from Philips TL 12 and TL 01 tubes[J]. Photodermatol Photoimmunol hotomed. 1994,10:22-25.
7. Van Weelden H,Baart diF,Young E,et al.Comparison of narrow-band UV-B phototherapy and PUVA photochemotherapy in the treatment of psoriasis[J].Acta Derm Venereol. 1990,70:212-215.
8. Enninga IC,Groenendijk RTL,Filon AR et al.The wavelength dependence of UV-induced pyrimidine dimmer formation,cell killing and mutation induction in human diploid skin fibroblasts[J].Carcinogenesis.1986,7:1829-1836.
9. You YH, Szabo PE, Pfeifer GP. Cyclobutane pyrimidine dimers form preferentially at the major p53 mutational hotspot in UVB-induced mouse skin tumors[J]. Carcinogenesis. 2000, 21(11 ):2113-2117.
1. Van de kerkhof PC.The Psoriasis Area and Severity Index and alternative approaches For theassessment of severity; persisting areas of confusion[J] .Br J Dermatol 1997;137(4):661-662.
2. Griffiths CEM. The immunological basis of psoriasis [J]. Eur Acad Dermatol Venereol 2003; 17(suppl2):1-5.
3. Chamian F, Krueger JG. Psoriasis vulgaris: an interplayof T lymphocytes, dendritic cells, and inflammatory cytokines in pathogenesis [J]. Curr Opin Rheumatol. 2004;16(4):331-337.
4. Gudjonsson IE, Johnston A, Sigmundsdottir H,ect. Immunopathogenic mechanisms in psoriasis [J]. Clin Exp Immunol. 2004; 135(1): 1-8
5. C.Green,J.Ferguson ,T.Lakshmipathi,ect.311nm UVB phototherapy-an effective treatment for psoriasis[J].Br.J.Dermatol. 1988(119):691-696.
6. B.A.Araneo,T.Dowell,H.Bac.Moon,ect.Regulation of murine lymphokine production in vivo.Ultraviolet radiation exposure depressesIL-2 and enhances IL-4 production by T cells through an IL-1 dependent mechanism[J].Immunol. 1989(143):1737-1744.
7. J.C.Simon,R.E.Tigelaar,P.R.Bergstresser,ect .Ultraviolet B radiation converts Langerhans cells from immunogenic to tolerogenic antigen-presentingcells[J].J Immunol. 1991 (146):485-491.
8. M. Tjioe, T. Smits,P. C. M. van de Kerkhof,ect.The differential effect of broad band vs.narrow band UVB with respect to photodamage and cutaneous inflammation, xperimental Dermatology [J]. 2003(12): 729-733.
9. Piskin G, Tursen U, Sylva-Steenland RMR, ect. Clinical improvement in chronic plaque-type psoriasis lesions after narrow-band UVB therapy is accompanied by a decrease in the expression of IFN-γinducers—IL-12, IL-18 and IL-23[J].Exp Dermatol 2004;13(12):764-772.
10. Arndt J.G.Schottelius,Lyle L.Moldawer,Charles A.Biology of tumor necrosis factor-αimplications for psoriasis[J].Experimental Dermatology 2004(13):193-222.
11. Serwin AB, Sokolowska M, Chodynicka B. Soluble tumor necrosis factor alpha receptor type 1 in psoriasis patients treated with narrowband ultraviolet B[J].Photodermatol Photoimmunol Photomed. 2005;21(4):210-211.
12. M.Simon,Jr and M.S.Gruschwitz,In situ expression and serum levels of tumor necrosis factor alpha receptors in patients with lichen planus[J].Acta Derm Venereol 1997(77): 189-191
13. Prinz JC. Which T cells cause psoriasis[J]? Clin Exp Dermatol. 1999; 24(4): 291-295.
14. De Rie MA, Goedkoop AY, Bos JD. Overview of psoriasis[J] . Demmto/ Tber. 2004;17(5):341-34
15. McKenzie RC, Sauder DN. The role of keratinocyte cytokines in inflammation and immunity [J]. Invest Dermatol. 1990;95(suppl 6):105S-107S.
16. Ozer Arican, Murat Aral, Sezai Sasniaz,ect.Serum Levels of TNF-α, IFN-γ, IL-6, IL-8, IL-12, IL-17,and IL-18 in Patients With Active Psoriasis and Correlation With Disease Severity[J]. Mediators of hiflammation . 2005 (5): 273-279
17. Schlaak JF, Buslau M, Jochum W et al: T cells involved in psoriasis vulgaris belong to the Th1 subset[J]. J Invest Dermatol, 1994(102): 145-49
18. Atamas SP, White B: Interleukin 4 in systemic sclerosis: not just an increase[J]. Clin Diag Lab Immunol, 1999(6): 658-659
19. Lowes MA, Lew W, Krueger ]C. Current concepts in the immunopathogenesis of psoriasis[J]. Dermatol Clin. 2004;22(4):349-369.
20. Shreedhar V, Giese T, Sung V W. A cytokine cascade including prostaglandin E2, IL-4, and IL-10 is responsible for UV-induced systemic immune suppression[J]. JImmunol 1998(160): 3783-3789.
1. Tjioe M, Smits T, van de Kerkhof PC, et al. The differential effect of broad band vs narrow band UVB with respect to photodamage and cutaneous inflammation. Exp Dermatol[J]. 2003,12(6):729-733.
2. Ozawa M, Ferenczi K, Kikuchi T, et al. 312-nanometer ultraviolet B light (narrow-band UVB) induces apoptosis of T cell within psoriatic lesions[J]. J.Exp.Med 1999,189(4): 711-718.
3. Piskin G, Sylva-Steenland RM, Bos JD, et al. T cells in psoriatic lesional skin that survive conventional therapy with NB-UVB radiation display reduced IFN-gamma expression[J]. Arch Dermatol Res 2004,295(12):509-516.
4. Horio T. Indications and action mechanisms of phototherapy [J]. J Dermatol Sci 2000 (23):S 17-21.
5. Kronauer C, Eberlein-Konig B, Ring J, et al. Influence of UVB, UVA and UVA1 irradiation on histamine release from human basophils and mast cells in vitro in the presence and absence of antioxidants [J]. Photochem Photobiol 2003, 77(5): 531-514.
6. Hart PH, Townley SL, Grimbaldeston MA, et al. Mast cells, neuropeptides, histamine, and prostaglandins in UV-induced systemic immunosuppression[J] . Methods 2002,28(1):79-89.
7. Bacci S, Alard P, Streilein JW, et al. Evidence that ultraviolet B radiation transiently inhibits emigration of Langerhans cells from exposed epidermis, thwarting contact hypersensitivity induction[J]. Eur J Immunol 2001,31(12):3588-3594
8. Ito T, Seo N, Yagita H, et al. Alterations of immune functions in barrier disrupted skin by UVB irradiation[J]. J Dermatol Sci2003,33(3):151-159.
9. Pupe A, Moison R, De Haes P, et al. Eicosapentaenoic acid, a n-3 polyunsaturated fatty acid differentially modulates TNF-alpha, IL-1 alpha, IL-6 and PGE2 expression in UVB-irradiated human keratinocytes[J]. J Invest Dermatol 2002,118(4):692-698.
10. Cather J, Menter A. Novel therapies for psoriasis[J]. Am J Clin Dermatol 2002,3(3):159-173.
11. Jones CD, Guckian M, el-Ghorr AA, et al. Effects of phototherapy on the production of cytokines by peripheral blood mononuclear cells and on systemic antibody responses in patients with psoriasis[J]. Photodermatol Photoimmunol Photomed 1996,12(5):204-210.
12. Piskin G, Koomen CW, Picavet D, et al. Ultraviolet-B irradiation decreases IFN-gamma and increases IL-4 expression in psoriatic lesional skin in situ and in cultured dermal T cells derived from these lesions[J]. Exp Dermatol 2003,12(2):172-180.
13. Piskin G, Tursen U, Bos JD,et al. IL-4 experssion by netrophils in psoriasis lesional skin upon high-dose UVB exposure[J]. Dermatology 2003,207(1): 51-53.
14. Ding W, Beissert S, Deng L, et al. Altered cutaneous immune parameters in transgenic mice overexpressing viral IL-10 in the epidermis[J]. J Clin Invest 2003,111(12):1923-1931.
15. Shen J, Bao S, Reeve VE. Modulation of IL-10, IL-12, and IFN-gamma in the epidermis of hairless mice by UVA (320-400 nm) and UVB (280-320 nm) radiation[J]. J Invest Dermatol 1999,113(6):1059-1064.
16. Piskin G, Tursen U, Sylva-Steenland RM. Clinical improvement in chronic plaque-type psoriasis lesions after narrow-band UVB therapy is accompanied by a decrease in the expression of IFN-gamma inducers - IL-12, IL-18 and IL-23[J]. Exp Dermatol 2004,13(12):764-772.
17. Hong K, Chu A, Ludvikkson BR, et al. IL-12, independently of IFN-gamma, plays the crucial role in the pathogenesis of a murine psoriasis-like skin disorder[J]. J Immunol 1999,162(12): 7480-7491.
18. Walters, Ian B, Ozawa Maki, et al. Narrow band (312nm) UVB suppresses interferon-gamma and interleukin(IL)-12 and increases IL-4 transcripts: differential regulation of cytokines at the single-cell level[J]. Arch of Dermatol 2003,139(2):155-161.
19. Cadet J, Douki T , Pouget JP , et al . Singlet oxygen DNA damage products : formation and measurement[J] . Methods Enzymol 2000,319:143-153.
20. Enninga IC,Groenendijk RTL,Filon AR et al.The wavelength dependence of UV-induced pyrimidine dimmer formation,cell killing and mutation induction in human diploid skinfibroblasts[J].Carcinogenesis 1986(7):1829 -1836.