慢性光化性皮炎的诊断及治疗课件

1、男性，27岁男，65岁慢性光化性皮炎的诊断及治疗广州市皮肤病防治所主讲人：陈荃、朱慧兰0102目录03慢性光化性皮炎的几个基本概念慢性光化性皮炎的诊断慢性光化性皮炎的防治及其进展慢性光化性皮炎的几个基本概念011. 什么是慢性光化性皮炎？ 慢性光化性皮炎(CAD)是一组以慢性光敏感为特征的免疫介导的病谱性疾病，包括持久性光反应（PLR）、光敏性湿疹（PE）、光敏性皮炎(PD)、光线性类网组织细胞增生症(AR)，其中PD和AR为病谱两端。 Chronic actinic dermatitis(CAD), previously known a persistent lightreaction, p

2、hotosensitive eczema, , photosensitivity dermatitis, and actinicreticuloid is an immunologically mediated photodermatosis characterizedby pruritic eczematous lesions of sun-exposed areasChronic Actinic Dermatitis, Dermatol Clin 32 (2014) 355361. Haxthausen first described this condition in 1933 in a

3、 patient withhypersensitivity to light after intravenous trypaflavine吖啶黄, a photosensitizingdye. Actinic reticuloid and two milder forms of CAD, referred to as photosensitiveeczema and photosensitivity dermatitis, were reported in 1969. By 1979, Hawk and Magnus had introduced the term “chronic actin

4、icdermatitis,” but it was not until 1990, when Lim and colleagues suggestedunifying the variants under the same name, that the term became widelyacceptedPhotodermatoses, including phototoxic and photoallergic reactions (internal and external), Clin Dermatol.2014;32(1):73-9.历史 （HISTORY）流行病学(EPIDEMIOL

5、OGY)CAD在美国、欧洲、亚洲、非洲均有报导，CAD在光照较强的夏天发病率较高CAD has been reported in the United States, Europe, Asia, and Africa, with increasedincidence in the summertime when sun exposure is greatest好发于年龄50岁的户外工作或喜户外运动男性，好发于Fitzpatrick分型V、VI的个体（美国报导）It commonly affects men older than 50 years who work or enjoy the ou

6、tdoors. Thiscondition can affect individuals of all skin types, although in the United States it is morecommonly reported in persons with Fitzpatrick skin types V and VI 本病无家族遗传史There is no familial inheritance.Association with HIV infection has been reported; as a group, these patients tend to beyo

7、unger than CAD patients without HIV infection.CAD发病率为1/6000，且发病率呈逐渐上升趋势对英国苏格兰首诊为CAD的128例患者统计发现，80%患者为60岁以上，且78%为男性Chronic Actinic DermatitisJ. Dermatol Clin,2014,32(3):355-61.Chronic Actinic Dermatitis in the Elderly Recognition and TreatmentJ.Drugs Aging,2005,22(3):201-7.2. 慢性光化性皮炎的病因及发病机制？紫外线 是主要致

8、病病因 致病光谱包括UVA、UVB和可见光 严格防晒是防治CAD的关键手段之一病因不同国家CAD患者光试验结果均提示对UVA+UVB最为敏感Chronic actinic dermatitis in Asian skin: a Singaporean experienceJ.Photodermatol Photoimmunol Photomed.2011,27(4):172-5.一项对亚洲CAD患者的光试验结果同样显示：UVB(39.7%)UVA(5.1%)UVA+UVB(55.2%)Chronic actinic dermatitis in Asian skin: a Singaporean

9、 experienceJ.Photodermatol PhotoimmunolPhotomed,2011,27(4):172-5. 变应原70%的CAD患者（光）斑贴试验可呈阳性避免接触过敏性变应原是防治CAD的关键手段之一Contact and photocontact sensitization in chronic actinicdermatitis: a changing picture.J. Contact Dermatitis.2010,62(1):42-6.光过敏原阳性率百份比三氯碳酰替苯胺盐酸氯丙嗪1.04氨基苯甲酸345三溴水杨酸苯胺盐酸氯丙嗪0.12羟基4甲氧基苯甲酮6甲基

10、香豆素硫双二氯酚硫双对氯酚松萝酸0.81%38.21%1.63%1.63%20.33%4.88%7.32%3.25%12.20%3.25%我所光斑贴试验的检出情况（123例）光过敏原阿托宁木材混合物地钱酸秘鲁香脂四氯水杨酸基酰苯胺六氯酚葡萄糖酸洗必泰三氯生盐酸苯海拉明香料香混合物阳性率百份比3.25%2.44%2.44%14.63%4.88%3.25%4.07%1.63%4.07%27.64%发病机制（PATHOGENESIS）CAD的发病机制尚不完全清楚，研究发现可能与以下机制相关The pathogenesis of CAD has not been completely elucidat

11、edCAD真皮中主要以CD8+ T细胞浸润，类似于变应性接触性皮炎存在粘附分子激活模式The clinical and histologic features, the presence of mostly CD81 T cells in the dermis, andthe pattern of adhesion molecule activation in CAD resemble allergic contact dermatitis.CAD是对光诱导的内源性抗原产生的一种迟发型超敏反应，是长期持续存在于皮肤中的外源性光敏剂所诱发的反应Thus, a mechanism of delay

12、ed-type hypersensitivity can be inferred. However, rather thanan exogenous agent, the cutaneous antigen is likely endogenous and photoinduced.Chronic Actinic DermatitisJ. Dermatol Clin,2014,32(3):355-61.Daiagnosis and treatment of chronic actinic dermatitisJ.Dermatol Ther,2003,16(1):45-51. MMP-1表达升高

13、与CAD中弹性组织变型的物质，如弹性蛋白及原纤维蛋白-1相关，提示可能参与其发病 丝聚蛋白可阻止过敏原渗透和促进光保护，在维持表皮的屏障功能发挥重要作用，提示丝聚蛋白可能参与CAD发病，但研究发现二者之间无较强关联，需进一步实验证实 The antigenic molecule in CAD has been theorized to be DNA, whichabsorbs UV radiation and is the molecule thought to be involved in sunburn. The action spectrum for CAD is similar to

14、that for sunburn, but at lowerdosesLoss-of-Function Mutations in the Gene Encoding Filaggrin Are NotStrongly Associated with Chronic Actinic DermatitisJ. InvestDermatol,2015,135(7):1919-21.3. 慢性光化性皮炎的临床表现（ ClinicalManifestations ）？CAD表现为分布于面部、颈部、手背、头皮和上胸部的湿疹样斑块，通常在衣服边线处有清晰的分界线。也可能观察到苔藓样变及红斑样浸润性丘疹和斑块

15、Skin findings of CAD include eczematous and often lichenified pruriticpatches and confluent plaques limited to sun-exposed areas of the scalp,face, neck, chest, arms, hands, and back, with notable sparing of sun-protected areas, such as nasolabial folds, submental chin, upper eyelids,retroauricular

16、areas, skin creases, and finger web spaces. Acute flares areassociated with erythematous patches and papules with fine scale on sun-exposed areasFig. 1. Clinical features of chronic actinic dermatitis (CAD).(A)(B)Erythema, lichenification, and scale on sunexposed skin. Note sparing ofpostauricular a

17、rea.Lichenification of sun-exposed sites, with sharp cutoff of sun-protected areas of theskin.双手背大片浸润性暗红色斑块，额部浸润性暗红色斑块，皮纹减少散在红色丘疹、结节郑跃，赖维， 苏向阳等.慢性光化性皮炎1例J.实用皮肤病学杂志,2009，2(3)：170-171.Fig. 2. Acute flare 24 hours after inadvertent sunexposure in a patient with CAD. Note diffuse erythemaon the face and

18、 superficial erosions on the nose.Fig. 3. Hyperkeratosis and scale on palms of a patient withCAD.rarely, erythroderma and hyperkeratosis ofpalms and soles may be observed病变最初只出现于光暴露的皮肤，但该病也可在数年内进展至未暴露的区域。严重病例可能出现全身性红皮病In severe cases, papules and plaques may occur on sunprotectedsites,albeit to a le

19、sser extent than on sun-exposed areas组织病理学表现（ Histology ）CAD病理显示海绵水肿性皮炎伴有淋巴细胞与组织细胞浸润及不同程度的棘层肥厚Pathologic examination of CAD demonstrates spongiotic dermatitis withlymphohistiocytic infiltrate and variable acanthosis.某些标本出现不典型淋巴细胞和胞外分泌，与皮肤T细胞淋巴瘤的组织学改变类似Atypical lymphocytes and exocytosis seen in some

20、 specimens may mimichistologic changes of CTCL. Papillary dermal fibrosis and a brisk infiltrate,both histologic signs of chronicity, may also be found. In severe cases thebiopsy may show focal epidermal necrosis, papillary dermal collagen, fibrindeposition in the dermal-epidermal junction, and eros

21、ions.淋巴细胞浸润； 倍。 图4 斑）： 化过度伴角栓，表皮增生，颗HE100 ：额部（红 角片1：前臂（红斑）：角化过度伴局灶角化不全，表皮增图片2：前臂（红斑）：角化过度伴局灶角化不全，表皮增生，颗粒层增厚，真皮浅层胶原轻度嗜碱性变，血管周围散在生，真皮内血管周围散在淋巴细胞浸润；HE40 性变图片3：额部（红斑）：角化过度伴角栓，表皮增生，表皮突下延，局部棘细胞间轻度水肿，真皮浅层胶原嗜碱 倍。 ，血管周围散在淋巴细胞为主炎细胞浸润；40倍。粒层增厚，表皮突下延，真皮浅层胶原嗜碱性变，血管周围散在淋巴细胞为主炎细胞浸润。HE40倍。有时可见真皮乳头纤维化和显著炎症细胞浸润等慢性组织学

22、表现Papillary dermal fibrosis and a brisk infiltrate, both histologic signs ofchronicity, may also be found.严重病例病理可见灶性表皮坏死、真皮乳头纤维化及纤维蛋白在表皮-真皮连接处沉积In severe cases the biopsy may show focal epidermal necrosis, papillarydermal collagen, fibrin deposition in the dermal-epidermal junction, anderosions.特征数量

23、（%）棘层肥厚37/37（100）海绵形成37/37（100）淋巴细胞浸润37/37（100）真皮乳头纤维组织增生37/37（100）黑素-巨噬细胞37/37（100）多核树突细胞35/37（95）浆细胞、嗜酸性粒细胞33/37（89）角化不全31/37（84）弹性纤维变形23/37（62）+CD8浸润20/25（80）+CD4浸润5/25(20) Sidiropoilos M等对37例CAD患者的组织病理特征进行总结：Chronic Actinic Dermatitis/Actinic Reticuloid:A Clinicopathologic and Immunohistochemica

24、l Analysis of 37 CasesJ.AM JDermatopathol,2014,36(11):875-81.慢性光化性皮炎的诊断02从哪些方面来诊断慢性光化性皮肤病？病史采集：注意光暴露体格检查：注意皮损特征光生物学试验：帮助诊断及鉴别实验室检查：协助诊断及鉴别诊断A systematic approach including pertinent history, physicalexamination, phototesting, photopatch testing, and laboratoryinvestigation are essential steps in eva

25、luating a photosensitive patientPhotodermatoses: diagnosis and treatment. Lehmann P, Schwarz T, Dtsch Arztebl Int. 2011 Mar;108(9):135-41.1. 慢性光化性皮炎的诊断依据？CAD的诊断依据：临床表现主要累及年龄较大患者的日光暴露皮肤的湿疹样和/或浸润性丘疹、斑块样皮疹，组织病理无特异性、类似于皮炎湿疹以及通过光试验发现对UVB+UVA(常见) 、UVB和可见光(偶尔)的敏感性增加(MED减小)，光斑贴试验提示对某些接触性光敏物质呈阳性。光暴露部位出现皮炎湿疹样

26、损害和/或浸润性丘疹、斑块，偶成红皮病；皮损持续3个月以上，反复发作，逐渐加重；好发于中老年男性1992年上海华山医院针对我国的CAD，提出了以下诊断标准：满足以上三个条件，经过长期随访和光生物学试验的验证，95%符合CAD诊断2. 如何进行患者评估和光生物学评估？ 全面的病史采集 完整的皮肤体格检查 患者评估包括：关注日光暴露和皮疹间的关系1发病年龄2光暴露至出现皮疹之间的时间长度、皮疹持续的时间3皮疹的部位4伴随症状(例如，瘙痒、疼痛、烧灼感，以及刺痛)5皮疹是否是由穿透窗户玻璃的日光暴露引起的6季节性变化7日光浴床的使用8职业性和娱乐性活动9光敏性的家族史、药物史(目前与既往的用药)、用

27、于皮肤的产品的使用史(暴露于光敏剂)、光加重性皮肤病的既往史1)病史采集（ A detailed history ）常见光毒性物质抗心律不齐药：奎尼丁利尿剂：呋塞米、噻嗪类非甾体类抗炎药：奈丁美酮、萘普生、吡罗昔康吩噻嗪类：氯丙嗪、丙氯拉嗪补骨脂素：5和8甲氧补骨脂素喹诺酮类：环丙沙星、洛美沙星、司巴沙星、奈啶酸金丝桃：金丝桃素四环素、多西环素常见光变应性物质外用制剂：防晒霜香料：6甲基香豆素、麝香葵子、檀香油消毒剂：流氯酚、氯已定、六氯酚抗心律不齐：奎尼定抗真菌药：辉煌霉素抗疟药：氯喹抗生素：喹诺酮类、磺胺类非甾体抗炎药：如酮洛芬玻璃窗 玻璃窗过滤后的紫外线是否引起皮疹为判断作用光谱提供信息

28、UVA、可见光可透过玻璃窗2)体格检查(Physical examination)皮肤检查应包括日光暴露区域和非暴露区域，特别关注日光暴露部位和光保护部位光暴露部位，皮疹通常对称性地发生于面部、双耳、颈部和胸部的“V”形区域，以及前臂伸肌侧光保护部位（气源性接触性皮炎），如上唇、颏下颈部、上睑、鼻唇沟耳廓后区域这些相对遮蔽的区域The physical examination should pay attention to the distribution of the lesionswith regards to sun-exposed/protected areas.皮疹的形态对于诊断非常

29、重要光试验-最小红斑量(MED)光斑贴试验光激发试验3)光生物学评估(Photobiological Evaluation)是评估光敏病人的必要组成Phototesting and occasionally photopatch testing areimportant parts of evaluationMED指在一定光源、距离的条件下，特定的个体、部位接受光照后24h产生肉眼观察所能见的红斑所需最小的剂量MED for UVA (MED-A) and UVB (MED-B), defined as the lowest dose of radiation thatproduces per

30、ceptible erythema covering the entire irradiated area, is determined.临床上采用UVB-MED或UVA-MED来分别表示患者对UVB或UVA的敏感程度在进行光试验时，使用具有多个开孔的不透光模板和适当的光源对皮肤的多个不同区域进行照射，并逐渐增加UVA、UVB或可见光的照射量采用未受累的部位(通常是背部或前臂内侧面)作为检测区域Phototesting is recommended for further evaluation of suspected CAD光试验-如果可进行光试验，可通过该试验测定患者的最小红斑量(mini

31、mal erythema dose, MED)MED测定光试验UVA（320-400nm）MED降低UVB（290-320nm）MED降低可见光（400-700nm）MED可能降低与正常对照相比，某些光感性皮肤病患者的MED较低光试验也有助于确定引起光感性皮肤病的光的波长(UVA、UVB或可见光)光试验操作的注意事项 选择非光暴露部位：背部、臀部、手臂内侧、腹部 抗组胺药、NSAIDs：测试前1-2天停药 皮质类固醇激素、补骨酯类、氯丙嗪、大剂量维生素：测试前1-2周停药 氯喹和其他免疫抑制剂：测试前=2周停药Classificationand evaluation of photoderma

32、toses. Dermatologic Therapy, Vol. 16, 2003, 17光试验的意义诊断：光敏感性、特发性光线性皮肤病 The initial use of phototesting is to establish the presence of a photosensitivity disorder andPhototesting is most helpful in the diagnosis of idiopathic acquired photodermatoses. It is not helpful in the evaluation of genodermat

33、oses, porphyrias, or nutritional deficiencies治疗：确定治病光谱和光疗初始治疗剂量 The most common action spectrum for CAD is UVB plus UVA, resulting in a decreasedminimal erythema dose (MED) for both UVB and UVA in most patients.随访：治疗后效果 However, CAD may be seen with decreased MED-B or MED-A alone (12%25%), or with a

34、combination of sensitivity to UVB, UVA, and visible light光斑贴试验对疑似存在局部光变应原(光变态反应)的患者有帮助Patch testing and photopatch testing may also be considered if warranted by thehistory of the patient. Patients with CAD in the United Kingdom often demonstratepositive patch testing to relevant Compositae, presuma

35、bly resulting from exposurefrom gardening.Photopatch testing: recommendations for a European photopatch test baseline series.Contact Dermatitis. 2013 Apr;68(4):239-43.光斑贴试验(photopatch testing)将两组相同的可能的光变应原放置于患者背部。移除其中1组，并使用5-10J/cm2剂量的UVA对该部位进行照射。再次覆盖该区域。24h后对照射区域和对照试验区域的反应进行检查。24h后分级反应?/+（可疑反应）红斑+（

36、弱阳性反应）红斑和浸润+（强阳性反应）红斑、浸润、丘疹、水疱+（极阳性反应）糜烂、大疱光斑贴试验反应分级类型非照射部位UVA照射部位接触性反应正常+光变态反应+同时存在接触性反应光变态反应+正常-光斑贴试验结果判读光生物学试验流程4)实验室检查(Laboratory Evaluation) ANA、ENA、卟啉、HLA分型、皮肤活检 Lupus serologies, such as antinuclear antibody (ANA) and anti-Ro/anti-Laantibodies, may be obtained and should be negative. Sezary-l

37、ike cells may beseen in erythrodermic CAD, but the CD4:CD8 ratio will be low and T-cell clonalitywill be absent.36 In addition, testing for HIV is recommended, especially inyounger patients, in whom CAD may be a presenting sign of HIV.Abbreviations: ANA, antinuclear antibody; CAD, chronic actinic de

38、rmatitis; CTCL, cutaneous T-cell lymphoma; CTD,connective tissue diseases; HIV, human immunodeficiency virus;MED, minimal erythema dose; UVA, ultraviolet A; UVB,ultravioletChronic Actinic Dermatitis with Leonine Facies and Iatrogenic Adrenal Insufficiency Successfully Treated with Topical Tacrolimus

39、J.Case RepDermatol,2011,3(1):49-54.慢性光化性皮炎的防治及其进展031.避光-严格的光防护是治疗光敏感性皮肤病的关键( Strict photoprotection is key in themanagement of CAD )避免日晒、避免正午日晒(10:00至16:00)穿防护服：长袖衬衫和长裤，宽檐帽Patients should be advised to wear broadspectrum (UVA and UVB) sunscreen witha minimum sun-protection factor of 30, long-sleeved

40、 clothing, and wide-brimmedhats, and to seek shade during peak hours (between 10 AM and 4 PM).汽车和住所使用可阻挡UVR的窗贴膜使用防晒指数不低于30的广谱防晒霜(同时防护UVA和UVB)，只有在斑贴和光斑贴试验排除防晒剂过敏后才能使用Clear museum films or UVA filters may be applied to windows to block most UVtransmission.38 It should be noted that there is no evidenc

41、e that television andcomputer screens might exacerbate this condition 防晒霜 对于光敏性患者，尤其是那些对紫外区照射敏感的患者，日常使用防晒霜很重要 防晒霜可分为化学类(有机类)和物理类(无机类)产品 化学类防晒霜可提供对紫外区辐射的防护 物理类防晒霜具有阻挡紫外辐射和某些可见光的能力 化学类防晒霜 化学类防晒霜的有效成分是通过吸收紫外辐射发挥作用的，具有不同的紫外线吸收谱。可吸收UVB范围内紫外线的防晒霜中所含的化学成分举例如下：肉桂酸盐类、水杨酸盐类、二苯甲酮类、氰双苯丙烯酸辛酯、甲酚曲唑三硅氧烷、亚甲基-双-苯并三唑基

42、四甲基丁基酚可吸收UVA范围内紫外线的化学类防晒霜的实例包括：二苯甲酮(吸收短波长的UVA)、阿伏苯宗、邻氨基苯甲酸甲酯、依莰舒(、甲酚曲唑三硅氧烷、亚甲基-双-苯并三唑基四甲基丁基酚、双-乙基己氧苯酚甲氧苯基三嗪。 物理类防晒霜 物理阻隔性(无机)防晒霜，如二氧化钛和氧化锌，是通过反射和散射紫外和可见光辐射发挥作用的这些成分的颗粒较大，使其不透明，这可使其阻挡某些可见光，但可能使其在美观上不被患者所接受目前已开发出了钛和氧化锌的透明性微粒化制剂。但一旦微粒化，这些成分对可见光和波长较长的UVA的散射能力减弱对于对可见光敏感的光感性皮肤病患者，如果采用物理阻挡性防晒霜作为避免日晒的一种辅助措施

43、并穿防晒服，应使用不透明的非微粒化制剂为CAD的一线治疗根据疾病严重程度和部位选择合适的强度Mid-potency to highpotency topical corticosteroids are effective for thecontrol of disease flare主要药理作用为抑制免疫和炎症反应具有疗效好、见效快的优点，患者容易接受，依从性较好如果药物选择不当或使用时间过长，可导致局部皮肤变薄、萎缩，毛细血管扩张，甚至突然停药后的病情反 弹现象However, the potential risks of skin atrophy, striae, and dyspigme

44、ntationpreclude their long-term use.2.药物治疗-局部1）外用糖皮质激素- In addition to photoprotection, patients may usetopical corticosteroids or topical calcineurin inhibitors as first-line therapy.2）外用钙调磷酸酶抑制剂-In addition to photoprotection, patients may use topicalcorticosteroids or topical calcineurin inhibito

45、rs as first-line therapy.大量病例证实1日2次外用0.1%他克莫司或吡美莫司治疗CAD有效，长期使用也不会引 起皮肤萎缩等不良反应Many case reports and case series support the therapeutic benefit of topical tacrolimus0.1% ointment, daily to twice daily, for CAD.作用机制与连接FK506蛋白、阻止活化的T细胞核因子脱磷酸化和IL2以及其它炎症因子的转录、抑制朗格汉斯细胞从而抑制T细胞活化有关Tacrolimus (Protopic) bind

46、s to FK506-binding protein, blocking dephosphorylation ofnuclear factor of activated T cells, and preventing transcription of interleukin-2 and otherinflammatory cytokines. In CAD, this seems to work by inhibiting T-lymphocyte activation bysuppressing Langerhans cells.应告知患者外用他克莫司或吡美莫司有增加皮肤恶性肿瘤和淋巴瘤的风

47、险Similar results have been achieved with topical pimecrolimus (Elidel) cream for CAD.48Patients must be informed of the black-box warning for increased risk of cutaneousmalignancy and lymphoma with topical tacrolimus and pimecrolimus, although convincingevidence is lacking.他克莫司局部外用6周后疗效对比图Chronic Ac

48、tinic Dermatitis with Leonine Facies and Iatrogenic Adrenal InsufficiencySuccessfully Treated with Topical Tacrolimus.Case Rep Dermatol 2011;3:4954 对于慢性或较肥厚的皮损应选用较为强效的外用糖皮质激素，短期内控制病情后，改用弱效的制剂或非糖皮质激素类药物 联合维 A 酸制剂外用则可减轻糖皮质激素产生的皮肤萎缩系统药物治疗-抗组胺药 日光性荨麻疹的一线治疗 优先使用第二代H1受体拮抗剂，剂量应高于常规使用剂量，以皮损控制为有效剂量 用于其他的光敏感性

49、皮肤病，仅有止痒效果氯喹羟氯喹具有抑制免疫反应、抗炎、光保护等作用用量：0.20.4g/天(All patients received either HC 400 mg daily for the firstmonth and 200 mg thereafter)可能引起视网膜病变、视敏度降低等眼部损害， 损害的发生与累积剂量、每日剂量有关每日剂量6.5 mg/kg 或总剂量100 g 者可引发眼部损害，应定期随访眼底情况抗疟药促进细胞调亡，有助于清除自身反应性淋巴细胞和减少自身/新抗原的递呈细胞核细胞质抗疟药可抑制细胞介导的细胞毒性抗疟药具有UV吸收特性，抑制UV诱导的磷脂酶A和C活性，降低

50、前列腺素合成从而发挥抗炎作用。抗疟药也可清除自由基、抑制阳光诱导的TNF、IL-1、IL-6和ICAM-1的表达，从而反向抑制炎性介导的损伤.羟氯喹治疗作用机制？阳光抗疟药在溶酶体内浓聚使PH升高，导致:1)稳定溶酶体2)抑制溶酶体内蛋白酶活性3)抑制膜受体再利用4)通过抑制多肽类与主要组织相容性复合体蛋白相结合，抑制抗原递呈细胞毒性T细胞HCQ抗疟作用-干扰DNA合成 与DNA结合，抑制DNA复制及RNA的转录，并使RNA断裂 抗疟原虫、抗细菌、抗病毒、抗真菌抑制DNA复制抑制RNA转录使RNA断裂静电作用 形成DNA-氯喹复合物稳定而不易解聚干扰蛋白质合成氯喹啉环影响疟原虫的繁殖免疫调节作

51、用 HCQ通过改变溶酶体和蛋白水解酶的PH值干扰抗原的加工，从而抑制抗原提呈过程抗原提呈免疫细胞免疫反应抗原功能障碍风湿免疫性疾病抗原提呈细胞（巨噬细胞）HCQToll样受体识别侵入体内的微生物，激活免疫细胞的应答。被认为在免疫系统中起关键作用HCQ阻断 TLR-7 and TLR-9 活化抑制Toll样受体信号目前研究的最新亮点可能是HCQ对很多自身免疫病具有作用的原因抗原提呈细胞（巨噬细胞）Nat Immunol. 2001 Aug;2(8):675-80Arthritis Rheum 2006;54: 3068HCQ炎症血管翳滑膜巨噬细胞软骨细胞T细胞IL-6IL-1IL-1IL-8TN

52、F-IL-6HCQ破骨细胞成纤维细胞生产MMPs和其它效应分子多形核白细胞的迁移骨和软骨侵蚀Ben-Zvi, I.et al.Hydroxychloroquine: From Malaria to Autoimmunity. Clin Rev Allergy Immunol, 2011.Br J Derm 2008; 159:1124HCQ调节细胞因子阻断单核细胞/巨噬细胞中的TNF-、IL-1- 和IL-6的产生HCQ对皮肤的保护浓集于皮肤吸收UV参与黑色素的代谢抑制皮肤受UV照射后所出现的DNA变性、胸腺嘧啶二聚体及抗DNA抗体的形成调节UV引起的原癌基因的活化HCQ被临床医生称为SLE病

53、人的避光剂吴东海,王国春主编. 临床风湿病学. 人民卫生出版社 2008,114-116缓解RA和SLEDE 关节炎和血管炎抑制血小板粘附和聚集，使血栓减小，降低心血管疾病风险吴东海,王国春主编. 临床风湿病学. 人民卫生出版社 2008,114-116HCQ的抗炎作用白三烯前列腺素PG介导疼痛、炎症和发热反应HCQ脂氧化酶磷脂磷脂酶A花生四烯酸抑制血栓素A促血小板凝聚形成血栓沙利度胺 50-200mgd 副作用：致畸（男女患者都应该避孕）、外周神经病、血栓形成等 Only single case reports exist to support the treatment ofrefract

54、ory CAD with low-dose thalidomide54 and interferon-a.口服沙利度胺5个月后疗效对比图推荐用法为：口服沙利度胺100g/d，逐渐减量为50mg，每周两次Recalcitrant chronic actinic dermatitis treated with low-dose thalidomide.J Am Acad Dermatol.2005 May;52(5):E6.糖皮质激素口服或者注射糖皮质激素，常用于严重急性发作患者的病情控制；一般口服强的松 0.5-1.0mg/（kg*d），两周之内减药Oral corticosteroids (p

55、rednisone 0.51.0 mg/kg/d) can be given for several weeks at a timefor flares.不良副作用较多：包括体重增加、高血糖、骨质疏松、青光眼、感染等Chronic steroid use is not recommended because of its adverse side-effect profile, including,but not limited to, weight gain, high blood sugar, increased risk for infections, osteoporosis,and

56、fractures, adrenal gland suppression, delayed wound healing, glaucoma or cataracts, andsteroid psychosis. Other steroid-sparing agents with proven efficacy in the treatment of CADinclude: cyclosporine (3.55 mg/kg/d), azathioprine (1.02.5 mg/kg/d)and mycophenolatemofetil (2540 mg/kg/d or 12 g/d)不建议长期

57、使用Patients should be counseled on the increased risk of infection with these medications.Additional potential side effects are noted in Table 1.免疫抑制剂严重病例或治疗效果不佳时，可以应用免疫抑制剂，包括环孢素、硫唑嘌呤和MTX等Systemic immunosuppressive therapy is frequently used for widespread orrefractory disease.环孢素（3-4mg/kg/d）：监测血药浓度、

58、肝肾功能和血压硫唑嘌呤（50-100mg/d）：检测TPMT基因型，监测白细胞、肝肾功能等均可致畸，需要避孕对反复发作的 CAD，联合羟氯喹与糖皮质激素或硫唑嘌呤可增加疗效3. 光疗PUVA疗法、UVB和UVA光疗对CAD有效对于中/重度 CAD 患者，光疗可以达到预防和治疗的效果NB-UVB有突出的免疫抑制作用，由于其波长单一为 311 nm，不良反应少而治疗效果好NB-UVB 治疗前需行 MED 测定，并根据 MED 来决定治疗剂量研究发现：NB-UVB联合系统激素（1mg/Kg/day）治疗、吗替麦考酚酯联合PUVA可成功治疗CADChronic actinic dermatitis:

59、two patients with successful management using narrowbandultraviolet Bphototherapy with systemic steroidsJ.Therapie. 2011,66(5):453-7.Chronisch aktinische Dermatitis Therapie mit systemischer PUVA und Mycophenolatmofetil J. Hautarzt,2011,62(7):539-42.Tofacitinib citrate for the treatment of refractor

60、y, severe chronic actinic dermatitisJ.JAADCase Rep. 2016 ,21;3(1):4-6.A、C是托法替尼治疗前；B、D是托法替尼治疗后用量：5mg bid po*8w尤其是重度CAD，使用激素、羟氯喹、甲氨蝶呤、环孢素、霉酚酸酯、光疗等抵抗时可考虑使用托法替尼。抑制JAK3激酶的免疫抑制剂托法替尼联合治疗：吗替麦考酚酯+0.05J/cm2PUVA 4个月后疗效对比图Chronisch aktinische Dermatitis Therapie mit systemischer PUVA undMycophenolatmofetil J. H