Even before the recent development of biological agents文档格式.docx

1、localised areas such as the elbows or knees. For thesepatients, topical therapy may remain part of their therapeuticregimen whether or not they require additional treatmentsfor psoriatic arthritis. Even those treated with phototherapyor systemic therapies, including biologicals, have residuallesions

2、 that may require topical remedies.Topical corticosteroids remain the most widely prescribedmedications for plaque psoriasis. These range in strengthfrom weak, over-the-counter steroids such as 1% hydrocortisoneto superpotent corticosteroids, such as clobetasolpropionate, halobetasol propionate, bet

3、amethasone dipropionatein optimised base, and diflorasone diacetate inaugmented base （table 2）. The StoughtonCornell classificaclassificationranks the potency of topical corticosteroids on theirability to induce vasoconstriction.3 Topical corticosteroids areavailable in numerous vehicles including p

4、owders, sprays,lotions, solutions, creams, emollient creams, ointments, gels,and tape. Recently, clobetasol propionate and betamethasonevalerate have both been introduced in foam vehicles that arecosmetically elegant and should improve compliance.Different vehicles are used on different body sites.

5、Forexample, the scalp and other hair bearing areas are mosteasily treated with foams, solutions, and gels. Creams aremost useful for daytime use, and ointments, which are oftenmore effective but less appealing cosmetically, can be appliedat night. Two possible exceptions are the newer foamvehicles,

6、which have comparable clinical efficacy to ointments.4 5Side effects of topical corticosteroids, especially those thatcarry the superpotent categorisation, include cutaneousatrophy, development of striae, formation of telangiectasia,and a host of other local cutaneous effects such as theformation of

7、 an acneiform eruption known as perioraldermatitis on the face.6 7 Hypothalamicpituitaryadrenal（HPA） axis suppression can occur with prolonged use ofexcessive quantities of topical corticosteroids, particularly ifthey are occluded or if superpotent corticosteroids are usedcontinuously over large are

8、as of the body. However, thecutaneous side effects are more commonly problematic thansignificant HPA axis suppression, which is seldom an issue.8One of the most troubling features of topical corticosteroidsis that patients develop tachyphylaxis, a phenomenonwhereby medications that are highly effect

9、ive initially, loseefficacy with prolonged use. To avoid tachyphylaxis and theother side effects of topical corticosteroids, regimens havebeen developed in which superpotent corticosteroids areapplied twice daily for two weeks, after which they areapplied on weekends only. Strong topical corticoster

10、oidsshould also be avoided on the face and intertriginous sites,areas that are more prone to steroid side effects. The quantityof strong topical corticosteroids applied should be limited to50 or 60 g per week, and occlusion should be avoided excepton the scalp, palms, and soles. Strong corticosteroi

11、ds shouldbe avoided or used cautiously in children.The second most commonly used group of medicationsconsists of the vitamin D analogues. In the USA, calcipotrieneis available in ointment, cream, and solution formulations.This agent is applied twice daily and is most often used inconjunction with to

12、pical corticosteroids. Its commonest sideeffect is irritation, primarily on the face and intertriginoussites. If large quantities of calcipotriene are applied, absorptionof this vitamin D analogue can result in hypercalcaemia.9Consequently, less than 120 g should be used weekly. Topicalcalcitriol is

13、 available in other parts of the world and may beless irritating on the face and in intertriginous sites. Othervitamin D analogues such as tacalcitol are also being used forpsoriasis. Some vitamin D analogues are unstable, andconsequently, they should only be combined with othermedications that have

14、 been demonstrated not to affect theirstability.10 Phototherapy may inactivate vitamin D analoguesand, conversely, vitamin D analogues may block thetherapeutic component of ultraviolet light; thus these topicalagents should be applied after phototherapy, not before.11Tazarotene gel, a recently devel

15、oped topical retinoid forpsoriasis, is available in 0.05% and 0.1% gels and creams.Topical retinoids may reverse some of the cutaneous atrophycaused by topical corticosteroids12 but are associated withlocal cutaneous irritation. Thus, they are often prescribed incombination with topical corticostero

16、ids.13Older topical remedies of psoriasis such as anthralin andcoal tar are still in use. Because they are somewhatunpleasant to use, especially due to odour, product migration,and local irritation, they are less commonly prescribed thanthe aforementioned topical medications. Keratolytic preparation

17、ssuch as those containing salicylic acid and emollientsare also effective for removing the excess scale that troublesmany patients with psoriasis.LIGHT THERAPYSeveral forms of light therapy have been used to treatpsoriasis for hundreds of years. In the 1920s, WilliamGoeckerman combined the use of ul

18、traviolet B （UVB）phototherapy with topical application of tars.14 This inpatientpsoriasis regimen, known as the Goeckerman regimen, is stilloccasionally used, but outpatient regimens using UVBphototherapy with emollients have largely replaced theinpatient regimens.Broadband UVB phototherapy has also

19、 been in use sincethe 1920s. It has not been associated with the development ofskin cancers despite the concomitant application of tars,which are considered carcinogenic.15 This therapy remainsone of the safest treatments for cutaneous psoriasis, butrequires treatments at least three times per week

20、for severalmonths to be effective.The most effective wavelengths of UVB light used for thetreatment of psoriasis fall in a very narrow range, 311313 nm.16 17 This has led to the development of narrowbandphototherapy.16 In the few years that narrowband UVBphototherapy has been used, no increase in cu

21、taneousmalignancies has been reported. More experience will beneeded to firmly establish the safety of narrowband UVBphototherapy. The excimer laser is a powerful beam of308 nm light （another form of narrowband ultraviolet light）that has been used successfully to treat localised plaques ofpsoriasis

22、including those on the palms and soles.18In the 1970s, a powerful new treatment of psoriasis knownas PUVA was introduced. PUVA involves the ingestion ortopical application of a photosensitising medication, usually8-methoxypsoralen. Patients are then exposed to UVA, whichactivates the 8-methoxypsoral

23、en. Once activated, this drugcrosslinks DNA strands preventing replication of keratinocytesand induces death of activated T cells in skin.19 BathPUVA, a topical photosensitising method, involves immersionof either localised areas （such as the hands or feet） or thewhole body in water containing disso

24、lved 8-methoxypsoralencapsules prior to UVA exposure. The topical use of this agentis not associated with adverse systemic symptoms such asnausea. Psoriasis clears in most patients treated with PUVA.PUVA may also benefit psoriatic arthritis in some patients.20For optimal effect, patients are typical

25、ly treated two to threetimes per week for several months. PUVA is significantlymore effective than broadband UVB, but it is associated withthe development of squamous cell carcinomas of the skin.The risk of non-melanoma cutaneous malignancies increaseswith the number of treatments but are rare in da

26、rk skinnedpatients.21 Most recently, there have been unconfirmedreports of an increased risk of malignant melanomas thatcorrelates with the number of treatments and time of followup, the increased risk being noted 15 years after startiPUVA.22Climatotherapy, the oldest form of phototherapy involvinge

27、xposure to sunlight, is well established at a number ofclinics around the world. Perhaps the most successful is thepsoriasis treatment centre at the Dead Sea.23 At 300 m belowsea level, the Dead Sea is the lowest point on earth. Itsmineral content is greater than that of any other naturallyoccurring

28、 body of water on earth. The extra 300 m throughwhich sunlight has to pass, combined with the mineral hazeover the Dead Sea, results in light exposure that has provedhighly beneficial for psoriasis. Results are comparable withthose obtained with broadband UVB phototherapy.24SYSTEMIC THERAPYThe three

29、 approved systemic treatments for psoriasis are:methotrexate, acitretin, and ciclosporin. Their use, advantages,and disadvantages, are discussed below.MethotrexateMethotrexate, the oldest systemic therapy for psoriasis,remains one of the most effective treatments for psoriasisand psoriatic arthritis. It has a number of short term sideeffects including bone marrow toxicit