慢性光化性皮炎的診斷及治療課件

1、男性，27歲男，65歲慢性光化性皮炎的診斷及治療廣州市皮膚病防治所主講人：陳荃、朱慧蘭0102目錄03慢性光化性皮炎的幾個基本概念慢性光化性皮炎的診斷慢性光化性皮炎的防治及其進展慢性光化性皮炎的幾個基本概念011. 什么是慢性光化性皮炎？ 慢性光化性皮炎(CAD)是一組以慢性光敏感為特征的免疫介導的病譜性疾病，包括持久性光反應（PLR）、光敏性濕疹（PE）、光敏性皮炎(PD)、光線性類網組織細胞增生癥(AR)，其中PD和AR為病譜兩端。 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吖啶黃, 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.歷史 （HISTORY）流行病學(EPIDEMIOL

5、OGY)CAD在美國、歐洲、亞洲、非洲均有報導，CAD在光照較強的夏天發(fā)病率較高CAD has been reported in the United States, Europe, Asia, and Africa, with increasedincidence in the summertime when sun exposure is greatest好發(fā)于年齡50歲的戶外工作或喜戶外運動男性，好發(fā)于Fitzpatrick分型V、VI的個體（美國報導）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 本病無家族遺傳史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發(fā)病率為1/6000，且發(fā)病率呈逐漸上升趨勢對英國蘇格蘭首診為CAD的128例患者統(tǒng)計發(fā)現，80%患者為60歲以上，且78%為男性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發(fā)病機制？紫外線 是主要致

8、病病因 致病光譜包括UVA、UVB和可見光 嚴格防曬是防治CAD的關鍵手段之一病因不同國家CAD患者光試驗結果均提示對UVA+UVB最為敏感Chronic actinic dermatitis in Asian skin: a Singaporean experienceJ.Photodermatol Photoimmunol Photomed.2011,27(4):172-5.一項對亞洲CAD患者的光試驗結果同樣顯示：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. 變應原70%的CAD患者（光）斑貼試驗可呈陽性避免接觸過敏性變應原是防治CAD的關鍵手段之一Contact and photocontact sensitization in chronic actinicdermatitis: a changing picture.J. Contact Dermatitis.2010,62(1):42-6.光過敏原陽性率百份比三氯碳酰替苯胺鹽酸氯丙嗪1.04氨基苯甲酸345三溴水楊酸苯胺鹽酸氯丙嗪0.12羥基4甲氧基苯甲酮6甲基

10、香豆素硫雙二氯酚硫雙對氯酚松蘿酸0.81%38.21%1.63%1.63%20.33%4.88%7.32%3.25%12.20%3.25%我所光斑貼試驗的檢出情況（123例）光過敏原阿托寧木材混合物地錢酸秘魯香脂四氯水楊酸基酰苯胺六氯酚葡萄糖酸洗必泰三氯生鹽酸苯海拉明香料香混合物陽性率百份比3.25%2.44%2.44%14.63%4.88%3.25%4.07%1.63%4.07%27.64%發(fā)病機制（PATHOGENESIS）CAD的發(fā)病機制尚不完全清楚，研究發(fā)現可能與以下機制相關The pathogenesis of CAD has not been completely elucidat

11、edCAD真皮中主要以CD8+ T細胞浸潤，類似于變應性接觸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是對光誘導的內源性抗原產生的一種遲發(fā)型超敏反應，是長期持續(xù)存在于皮膚中的外源性光敏劑所誘發(fā)的反應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表達升高

13、與CAD中彈性組織變型的物質，如彈性蛋白及原纖維蛋白-1相關，提示可能參與其發(fā)病 絲聚蛋白可阻止過敏原滲透和促進光保護，在維持表皮的屏障功能發(fā)揮重要作用，提示絲聚蛋白可能參與CAD發(fā)病，但研究發(fā)現二者之間無較強關聯，需進一步實驗證實 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. 慢性光化性皮炎的臨床表現（ ClinicalManifestations ）？CAD表現為分布于面部、頸部、手背、頭皮和上胸部的濕疹樣斑塊，通常在衣服邊線處有清晰的分界線。也可能觀察到苔蘚樣變及紅斑樣浸潤性丘疹和斑塊

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.雙手背大片浸潤性暗紅色斑塊，額部浸潤性暗紅色斑塊，皮紋減少散在紅色丘疹、結節(jié)鄭躍，賴維， 蘇向陽等.慢性光化性皮炎1例J.實用皮膚病學雜志,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病變最初只出現于光暴露的皮膚，但該病也可在數年內進展至未暴露的區(qū)域。嚴重病例可能出現全身性紅皮病In severe cases, papules and plaques may occur on sunprotectedsites,albeit to a le

19、sser extent than on sun-exposed areas組織病理學表現（ Histology ）CAD病理顯示海綿水腫性皮炎伴有淋巴細胞與組織細胞浸潤及不同程度的棘層肥厚Pathologic examination of CAD demonstrates spongiotic dermatitis withlymphohistiocytic infiltrate and variable acanthosis.某些標本出現不典型淋巴細胞和胞外分泌，與皮膚T細胞淋巴瘤的組織學改變類似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.淋巴細胞浸潤； 倍。 圖4 斑）： 化過度伴角栓，表皮增生，顆HE100 ：額部（紅 角片1：前臂（紅斑）：角化過度伴局灶角化不全，表皮增圖片2：前臂（紅斑）：角化過度伴局灶角化不全，表皮增生，顆粒層增厚，真皮淺層膠原輕度嗜堿性變，血管周圍散在生，真皮內血管周圍散在淋巴細胞浸潤；HE40 性變圖片3：額部（紅斑）：角化過度伴角栓，表皮增生，表皮突下延，局部棘細胞間輕度水腫，真皮淺層膠原嗜堿 倍。 ，血管周圍散在淋巴細胞為主炎細胞浸潤；40倍。粒層增厚，表皮突下延，真皮淺層膠原嗜堿性變，血管周圍散在淋巴細胞為主炎細胞浸潤。HE40倍。有時可見真皮乳頭纖維化和顯著炎癥細胞浸潤等慢性組織學

22、表現Papillary dermal fibrosis and a brisk infiltrate, both histologic signs ofchronicity, may also be found.嚴重病例病理可見灶性表皮壞死、真皮乳頭纖維化及纖維蛋白在表皮-真皮連接處沉積In severe cases the biopsy may show focal epidermal necrosis, papillarydermal collagen, fibrin deposition in the dermal-epidermal junction, anderosions.特征數量

23、（%）棘層肥厚37/37（100）海綿形成37/37（100）淋巴細胞浸潤37/37（100）真皮乳頭纖維組織增生37/37（100）黑素-巨噬細胞37/37（100）多核樹突細胞35/37（95）漿細胞、嗜酸性粒細胞33/37（89）角化不全31/37（84）彈性纖維變形23/37（62）+CD8浸潤20/25（80）+CD4浸潤5/25(20) Sidiropoilos M等對37例CAD患者的組織病理特征進行總結：Chronic Actinic Dermatitis/Actinic Reticuloid:A Clinicopathologic and Immunohistochemica

24、l Analysis of 37 CasesJ.AM JDermatopathol,2014,36(11):875-81.慢性光化性皮炎的診斷02從哪些方面來診斷慢性光化性皮膚?。坎∈凡杉鹤⒁夤獗┞扼w格檢查：注意皮損特征光生物學試驗：幫助診斷及鑒別實驗室檢查：協助診斷及鑒別診斷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. 慢性光化性皮炎的診斷依據？CAD的診斷依據：臨床表現主要累及年齡較大患者的日光暴露皮膚的濕疹樣和/或浸潤性丘疹、斑塊樣皮疹，組織病理無特異性、類似于皮炎濕疹以及通過光試驗發(fā)現對UVB+UVA(常見) 、UVB和可見光(偶爾)的敏感性增加(MED減小)，光斑貼試驗提示對某些接觸性光敏物質呈陽性。光暴露部位出現皮炎濕疹樣

26、損害和/或浸潤性丘疹、斑塊，偶成紅皮??；皮損持續(xù)3個月以上，反復發(fā)作，逐漸加重；好發(fā)于中老年男性1992年上海華山醫(yī)院針對我國的CAD，提出了以下診斷標準：滿足以上三個條件，經過長期隨訪和光生物學試驗的驗證，95%符合CAD診斷2. 如何進行患者評估和光生物學評估？ 全面的病史采集 完整的皮膚體格檢查 患者評估包括：關注日光暴露和皮疹間的關系1發(fā)病年齡2光暴露至出現皮疹之間的時間長度、皮疹持續(xù)的時間3皮疹的部位4伴隨癥狀(例如，瘙癢、疼痛、燒灼感，以及刺痛)5皮疹是否是由穿透窗戶玻璃的日光暴露引起的6季節(jié)性變化7日光浴床的使用8職業(yè)性和娛樂性活動9光敏性的家族史、藥物史(目前與既往的用藥)、用

27、于皮膚的產品的使用史(暴露于光敏劑)、光加重性皮膚病的既往史1)病史采集（ A detailed history ）常見光毒性物質抗心律不齊藥：奎尼丁利尿劑：呋塞米、噻嗪類非甾體類抗炎藥：奈丁美酮、萘普生、吡羅昔康吩噻嗪類：氯丙嗪、丙氯拉嗪補骨脂素：5和8甲氧補骨脂素喹諾酮類：環(huán)丙沙星、洛美沙星、司巴沙星、奈啶酸金絲桃：金絲桃素四環(huán)素、多西環(huán)素常見光變應性物質外用制劑：防曬霜香料：6甲基香豆素、麝香葵子、檀香油消毒劑：流氯酚、氯已定、六氯酚抗心律不齊：奎尼定抗真菌藥：輝煌霉素抗瘧藥：氯喹抗生素：喹諾酮類、磺胺類非甾體抗炎藥：如酮洛芬玻璃窗 玻璃窗過濾后的紫外線是否引起皮疹為判斷作用光譜提供信息

28、UVA、可見光可透過玻璃窗2)體格檢查(Physical examination)皮膚檢查應包括日光暴露區(qū)域和非暴露區(qū)域，特別關注日光暴露部位和光保護部位光暴露部位，皮疹通常對稱性地發(fā)生于面部、雙耳、頸部和胸部的“V”形區(qū)域，以及前臂伸肌側光保護部位（氣源性接觸性皮炎），如上唇、頦下頸部、上瞼、鼻唇溝耳廓后區(qū)域這些相對遮蔽的區(qū)域The physical examination should pay attention to the distribution of the lesionswith regards to sun-exposed/protected areas.皮疹的形態(tài)對于診斷非常

29、重要光試驗-最小紅斑量(MED)光斑貼試驗光激發(fā)試驗3)光生物學評估(Photobiological Evaluation)是評估光敏病人的必要組成Phototesting and occasionally photopatch testing areimportant parts of evaluationMED指在一定光源、距離的條件下，特定的個體、部位接受光照后24h產生肉眼觀察所能見的紅斑所需最小的劑量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.臨床上采用UVB-MED或UVA-MED來分別表示患者對UVB或UVA的敏感程度在進行光試驗時，使用具有多個開孔的不透光模板和適當的光源對皮膚的多個不同區(qū)域進行照射，并逐漸增加UVA、UVB或可見光的照射量采用未受累的部位(通常是背部或前臂內側面)作為檢測區(qū)域Phototesting is recommended for further evaluation of suspected CAD光試驗-如果可進行光試驗，可通過該試驗測定患者的最小紅斑量(mini

31、mal erythema dose, MED)MED測定光試驗UVA（320-400nm）MED降低UVB（290-320nm）MED降低可見光（400-700nm）MED可能降低與正常對照相比，某些光感性皮膚病患者的MED較低光試驗也有助于確定引起光感性皮膚病的光的波長(UVA、UVB或可見光)光試驗操作的注意事項 選擇非光暴露部位：背部、臀部、手臂內側、腹部 抗組胺藥、NSAIDs：測試前1-2天停藥 皮質類固醇激素、補骨酯類、氯丙嗪、大劑量維生素：測試前1-2周停藥 氯喹和其他免疫抑制劑：測試前=2周停藥Classificationand evaluation of photoderma

32、toses. Dermatologic Therapy, Vol. 16, 2003, 17光試驗的意義診斷：光敏感性、特發(fā)性光線性皮膚病 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治療：確定治病光譜和光療初始治療劑量 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.隨訪：治療后效果 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光斑貼試驗對疑似存在局部光變應原(光變態(tài)反應)的患者有幫助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.光斑貼試驗(photopatch testing)將兩組相同的可能的光變應原放置于患者背部。移除其中1組，并使用5-10J/cm2劑量的UVA對該部位進行照射。再次覆蓋該區(qū)域。24h后對照射區(qū)域和對照試驗區(qū)域的反應進行檢查。24h后分級反應?/+（可疑反應）紅斑+（

36、弱陽性反應）紅斑和浸潤+（強陽性反應）紅斑、浸潤、丘疹、水皰+（極陽性反應）糜爛、大皰光斑貼試驗反應分級類型非照射部位UVA照射部位接觸性反應正常+光變態(tài)反應+同時存在接觸性反應光變態(tài)反應+正常-光斑貼試驗結果判讀光生物學試驗流程4)實驗室檢查(Laboratory Evaluation) ANA、ENA、卟啉、HLA分型、皮膚活檢 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進展031.避光-嚴格的光防護是治療光敏感性皮膚病的關鍵( Strict photoprotection is key in themanagement of CAD )避免日曬、避免正午日曬(10:00至16:00)穿防護服：長袖襯衫和長褲，寬檐帽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).汽車和住所使用可阻擋UVR的窗貼膜使用防曬指數不低于30的廣譜防曬霜(同時防護UVA和UVB)，只有在斑貼和光斑貼試驗排除防曬劑過敏后才能使用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 防曬霜 對于光敏性患者，尤其是那些對紫外區(qū)照射敏感的患者，日常使用防曬霜很重要 防曬霜可分為化學類(有機類)和物理類(無機類)產品 化學類防曬霜可提供對紫外區(qū)輻射的防護 物理類防曬霜具有阻擋紫外輻射和某些可見光的能力 化學類防曬霜 化學類防曬霜的有效成分是通過吸收紫外輻射發(fā)揮作用的，具有不同的紫外線吸收譜?？晌誙VB范圍內紫外線的防曬霜中所含的化學成分舉例如下：肉桂酸鹽類、水楊酸鹽類、二苯甲酮類、氰雙苯丙烯酸辛酯、甲酚曲唑三硅氧烷、亞甲基-雙-苯并三唑基

42、四甲基丁基酚可吸收UVA范圍內紫外線的化學類防曬霜的實例包括：二苯甲酮(吸收短波長的UVA)、阿伏苯宗、鄰氨基苯甲酸甲酯、依莰舒(、甲酚曲唑三硅氧烷、亞甲基-雙-苯并三唑基四甲基丁基酚、雙-乙基己氧苯酚甲氧苯基三嗪。 物理類防曬霜 物理阻隔性(無機)防曬霜，如二氧化鈦和氧化鋅，是通過反射和散射紫外和可見光輻射發(fā)揮作用的這些成分的顆粒較大，使其不透明，這可使其阻擋某些可見光，但可能使其在美觀上不被患者所接受目前已開發(fā)出了鈦和氧化鋅的透明性微?；苿?。但一旦微?；?，這些成分對可見光和波長較長的UVA的散射能力減弱對于對可見光敏感的光感性皮膚病患者，如果采用物理阻擋性防曬霜作為避免日曬的一種輔助措施

43、并穿防曬服，應使用不透明的非微?；苿镃AD的一線治療根據疾病嚴重程度和部位選擇合適的強度Mid-potency to highpotency topical corticosteroids are effective for thecontrol of disease flare主要藥理作用為抑制免疫和炎癥反應具有療效好、見效快的優(yōu)點，患者容易接受，依從性較好如果藥物選擇不當或使用時間過長，可導致局部皮膚變薄、萎縮，毛細血管擴張，甚至突然停藥后的病情反 彈現象However, the potential risks of skin atrophy, striae, and dyspigme

44、ntationpreclude their long-term use.2.藥物治療-局部1）外用糖皮質激素- In addition to photoprotection, patients may usetopical corticosteroids or topical calcineurin inhibitors as first-line therapy.2）外用鈣調磷酸酶抑制劑-In addition to photoprotection, patients may use topicalcorticosteroids or topical calcineurin inhibito

45、rs as first-line therapy.大量病例證實1日2次外用0.1%他克莫司或吡美莫司治療CAD有效，長期使用也不會引 起皮膚萎縮等不良反應Many case reports and case series support the therapeutic benefit of topical tacrolimus0.1% ointment, daily to twice daily, for CAD.作用機制與連接FK506蛋白、阻止活化的T細胞核因子脫磷酸化和IL2以及其它炎癥因子的轉錄、抑制朗格漢斯細胞從而抑制T細胞活化有關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.應告知患者外用他克莫司或吡美莫司有增加皮膚惡性腫瘤和淋巴瘤的風

47、險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周后療效對比圖Chronic Ac

48、tinic Dermatitis with Leonine Facies and Iatrogenic Adrenal InsufficiencySuccessfully Treated with Topical Tacrolimus.Case Rep Dermatol 2011;3:4954 對于慢性或較肥厚的皮損應選用較為強效的外用糖皮質激素，短期內控制病情后，改用弱效的制劑或非糖皮質激素類藥物 聯合維 A 酸制劑外用則可減輕糖皮質激素產生的皮膚萎縮系統(tǒng)藥物治療-抗組胺藥 日光性蕁麻疹的一線治療 優(yōu)先使用第二代H1受體拮抗劑，劑量應高于常規(guī)使用劑量，以皮損控制為有效劑量 用于其他的光敏感性

49、皮膚病，僅有止癢效果氯喹羥氯喹具有抑制免疫反應、抗炎、光保護等作用用量：0.20.4g/天(All patients received either HC 400 mg daily for the firstmonth and 200 mg thereafter)可能引起視網膜病變、視敏度降低等眼部損害， 損害的發(fā)生與累積劑量、每日劑量有關每日劑量6.5 mg/kg 或總劑量100 g 者可引發(fā)眼部損害，應定期隨訪眼底情況抗瘧藥促進細胞調亡，有助于清除自身反應性淋巴細胞和減少自身/新抗原的遞呈細胞核細胞質抗瘧藥可抑制細胞介導的細胞毒性抗瘧藥具有UV吸收特性，抑制UV誘導的磷脂酶A和C活性，降低

50、前列腺素合成從而發(fā)揮抗炎作用?？汞懰幰部汕宄杂苫?、抑制陽光誘導的TNF、IL-1、IL-6和ICAM-1的表達，從而反向抑制炎性介導的損傷.羥氯喹治療作用機制？陽光抗瘧藥在溶酶體內濃聚使PH升高，導致:1)穩(wěn)定溶酶體2)抑制溶酶體內蛋白酶活性3)抑制膜受體再利用4)通過抑制多肽類與主要組織相容性復合體蛋白相結合，抑制抗原遞呈細胞毒性T細胞HCQ抗瘧作用-干擾DNA合成 與DNA結合，抑制DNA復制及RNA的轉錄，并使RNA斷裂 抗瘧原蟲、抗細菌、抗病毒、抗真菌抑制DNA復制抑制RNA轉錄使RNA斷裂靜電作用 形成DNA-氯喹復合物穩(wěn)定而不易解聚干擾蛋白質合成氯喹啉環(huán)影響瘧原蟲的繁殖免疫調節(jié)作

51、用 HCQ通過改變溶酶體和蛋白水解酶的PH值干擾抗原的加工，從而抑制抗原提呈過程抗原提呈免疫細胞免疫反應抗原功能障礙風濕免疫性疾病抗原提呈細胞（巨噬細胞）HCQToll樣受體識別侵入體內的微生物，激活免疫細胞的應答。被認為在免疫系統(tǒng)中起關鍵作用HCQ阻斷 TLR-7 and TLR-9 活化抑制Toll樣受體信號目前研究的最新亮點可能是HCQ對很多自身免疫病具有作用的原因抗原提呈細胞（巨噬細胞）Nat Immunol. 2001 Aug;2(8):675-80Arthritis Rheum 2006;54: 3068HCQ炎癥血管翳滑膜巨噬細胞軟骨細胞T細胞IL-6IL-1IL-1IL-8TN

52、F-IL-6HCQ破骨細胞成纖維細胞生產MMPs和其它效應分子多形核白細胞的遷移骨和軟骨侵蝕Ben-Zvi, I.et al.Hydroxychloroquine: From Malaria to Autoimmunity. Clin Rev Allergy Immunol, 2011.Br J Derm 2008; 159:1124HCQ調節(jié)細胞因子阻斷單核細胞/巨噬細胞中的TNF-、IL-1- 和IL-6的產生HCQ對皮膚的保護濃集于皮膚吸收UV參與黑色素的代謝抑制皮膚受UV照射后所出現的DNA變性、胸腺嘧啶二聚體及抗DNA抗體的形成調節(jié)UV引起的原癌基因的活化HCQ被臨床醫(yī)生稱為SLE病

53、人的避光劑吳東海,王國春主編. 臨床風濕病學. 人民衛(wèi)生出版社 2008,114-116緩解RA和SLEDE 關節(jié)炎和血管炎抑制血小板粘附和聚集，使血栓減小，降低心血管疾病風險吳東海,王國春主編. 臨床風濕病學. 人民衛(wèi)生出版社 2008,114-116HCQ的抗炎作用白三烯前列腺素PG介導疼痛、炎癥和發(fā)熱反應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（男女患者都應該避孕）、外周神經病、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個月后療效對比圖推薦用法為：口服沙利度胺100g/d，逐漸減量為50mg，每周兩次Recalcitrant chronic actinic dermatitis treated with low-dose thalidomide.J Am Acad Dermatol.2005 May;52(5):E6.糖皮質激素口服或者注射糖皮質激素，常用于嚴重急性發(fā)作患者的病情控制；一般口服強的松 0.5-1.0mg/（kg*d），兩周之內減藥Oral corticosteroids (p

55、rednisone 0.51.0 mg/kg/d) can be given for several weeks at a timefor flares.不良副作用較多：包括體重增加、高血糖、骨質疏松、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)不建議長期

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.免疫抑制劑嚴重病例或治療效果不佳時，可以應用免疫抑制劑，包括環(huán)孢素、硫唑嘌呤和MTX等Systemic immunosuppressive therapy is frequently used for widespread orrefractory disease.環(huán)孢素（3-4mg/kg/d）：監(jiān)測血藥濃度、

58、肝腎功能和血壓硫唑嘌呤（50-100mg/d）：檢測TPMT基因型，監(jiān)測白細胞、肝腎功能等均可致畸，需要避孕對反復發(fā)作的 CAD，聯合羥氯喹與糖皮質激素或硫唑嘌呤可增加療效3. 光療PUVA療法、UVB和UVA光療對CAD有效對于中/重度 CAD 患者，光療可以達到預防和治療的效果NB-UVB有突出的免疫抑制作用，由于其波長單一為 311 nm，不良反應少而治療效果好NB-UVB 治療前需行 MED 測定，并根據 MED 來決定治療劑量研究發(fā)現：NB-UVB聯合系統(tǒng)激素（1mg/Kg/day）治療、嗎替麥考酚酯聯合PUVA可成功治療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是托法替尼治療前；B、D是托法替尼治療后用量：5mg bid po*8w尤其是重度CAD，使用激素、羥氯喹、甲氨蝶呤、環(huán)孢素、霉酚酸酯、光療等抵抗時可考慮使用托法替尼。抑制JAK3激酶的免疫抑制劑托法替尼聯合治療：嗎替麥考酚酯+0.05J/cm2PUVA 4個月后療效對比圖Chronisch aktinische Dermatitis Therapie mit systemischer PUVA undMycophenolatmofetil J. H