2009+BAD+接触性皮炎的管理指南更新

GUIDELINES BJD British Journal of Dermatology Guidelines for the management of contact dermatitis: an update J. Bourke, I. Coulson* and J. English� Department of Dermatology, South Infirmary, Victoria Hospital, Cork, Ireland *Department of Dermatology, Burnley General Hospital, Burnley, U.K. �Department of Dermatology, Queen’s Medical Centre, Nottingham University Hospital, Nottingham NG7 2UH, U.K. Correspondence John English. E-mail: john.english@nuh.nhs.uk Accepted for publication 10 December 2008 Key words contact dermatitis, guidelines, patch testing Conflicts of interest None declared. These guidelines represent an update, commissioned by the British Association of Dermatologists Therapy Guidelines and Audit Subcommittee: H.K. Bell (Chair), D.J. Eedy, D.M. Mitchell, R.H. Bull, M.J. Tidman, L.C. Fuller, P.D. Yesudian, D. Joseph and S. Wagle. The original guidelines were produced in 2001 by the British Association of Dermatologists and were reviewed and updated in April 2008. DOI 10.1111/j.1365-2133.2009.09106.x Summary These guidelines for management of contact dermatitis have been prepared for dermatologists on behalf of the British Association of Dermatologists. They pres- ent evidence-based guidance for investigation and treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, including details of relevant epidemiological aspects, diagnosis and investigation. Disclaimer These guidelines have been prepared for dermatologists on behalf of the British Association of Dermatologists and reflect the best data available at the time the report was prepared. Caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclu- sions or recommendations in this report. It may be necessary or even desirable to depart from the guidelines in the interests of specific patients and special circumstances. Just as adherence to guidelines may not constitute defence against a claim of negligence, so deviation from them should not necessarily be deemed negligent. Definition The words ‘eczema’ and ‘dermatitis’ are often used synony- mously to describe a polymorphic pattern of inflammation, which in the acute phase is characterized by erythema and vesiculation, and in the chronic phase by dryness, lichenifi- cation and fissuring. Contact dermatitis describes these pat- terns of reaction in response to external agents, which may be the result of the external agents acting either as irritants, where the T cell-mediated immune response is not involved, or as allergens, where cell-mediated immunity is involved. Contact dermatitis may be classified into the following reac- tion types: Subjective irritancy – idiosyncratic stinging and smarting reac- tions that occur within minutes of contact, usually on the face, in the absence of visible changes. Cosmetic or sunscreen constituents are common precipitants. Acute irritant contact dermatitis – often the result of a single overwhelming exposure or a few brief exposures to strong irritants or caustic agents. Chronic (cumulative) irritant contact dermatitis – this occurs follow- ing repetitive exposure to weaker irritants which may be either ‘wet’, such as detergents, organic solvents, soaps, weak � 2009 The Authors 946 Journal Compilation � 2009 British Association of Dermatologists • British Journal of Dermatology 2009 160, pp946–954 acids and alkalis, or ‘dry’, such as low humidity air, heat, powders and dusts. Allergic contact dermatitis – this involves sensitization of the immune system to a specific allergen or allergens with result- ing dermatitis or exacerbation of pre-existing dermatitis. Phototoxic, photoallergic and photoaggravated contact dermatitis – some allergens are also photoallergens. It is not always easy to dis- tinguish between photoallergic and phototoxic reactions. Systemic contact dermatitis – seen after the systemic administra- tion of a substance, usually a drug, to which topical sensitiza- tion has previously occurred. In practice, it is not uncommon for endogenous, irritant and allergic aetiologies to coexist in the development of cer- tain eczemas, particularly hand and foot eczema. It is impor- tant to recognize and seek in the history, or by a home or workplace visit, any recreational and occupational factors in irritant and allergic dermatitis. Other types of contact reactions are not discussed in these guidelines. Strength of recommendations and quality of evi- dence gradings are listed in Appendix 1. Epidemiology Properly designed and conducted studies to determine the prevalence of dermatitis in the general community are few but the point prevalence of dermatitis in the U.K. is estimated at about 20%, with atopic eczema forming the majority.1 The best studies show a point prevalence of hand dermatitis in South Sweden of 2%2 and the lifetime risk of developing hand eczema to be 20% in women.3 Irritant contact dermatitis is more common than allergic dermatitis; allergic dermatitis usu- ally carries a worse prognosis than irritant dermatitis unless the allergen is identified and avoided. Contact dermatitis accounts for 4–7% of dermatological consultations. Chronicity is commonest in those allergic to nickel and chromate. Occupational dermatitis remains a bur- den for those affected. The most recent THOR ⁄EPIDERM fig- ures indicate that skin disease follows mental illness and musculoskeletal problems as a cause of occupational disease and accounts for approximately one in seven reported work- related cases in the U.K.4 Occupational dermatitis makes up the bulk of occupational skin disease (approximately 70%) with a rate of 68 per million of the population presenting to dermatologists annually and 260 per million to occupational physicians who tend to see earlier and less severe skin disease. The number of reports of allergic contact dermatitis in chil- dren is increasing.5 The principle allergens which have been identified include nickel, topical antibiotics, preservative chemicals, fragrances and rubber accelerators. Children with eczematous eruptions should be patch tested, particularly those with hand and eyelid eczema6 (Quality of evidence II.ii) (Strength of recommendation A). Contact allergy to specific allergens has been estimated in the general population to be 4Æ5% for nickel,7 and 1–3% of the population are allergic to ingredient(s) of a cosmetic.8 The prevalence of allergy to the other common allergens in the general population is not known as almost all studies have patch tested selected groups rather than general populations. Who should be investigated? Many authors have identified the unreliability of clinical fea- tures alone in distinguishing allergic contact from irritant and endogenous eczema, particularly with hand and facial eczema.9–12 Patch testing is therefore an essential investigation in patients with persistent eczematous eruptions when contact allergy is suspected or cannot be ruled out (Quality of evidence II.ii) (Strength of recommendation A). A prospective study13 has confirmed the value of a specialist contact clinic in the diagno- sis of contact dermatitis. It highlighted the importance of for- mal training in patch test reading and interpretation, testing with additional series and prick testing in the investigation of patients with contact dermatitis (Quality of evidence II.i) (Strength of recommendation A). Referral rate An approximate annual workload for a contact dermatitis investigation clinic has been suggested to be one individual investigated per 700 of the population served14 (Quality of evi- dence II.ii) (Strength of recommendation B), i.e. 100 patients patch tested for every 70 000 of the catchment population per year. A positive linear relationship was found between the number of relevant allergic patch test reactions and the number of patients referred by individual consultants. Diagnostic tests Patch testing The mainstay of diagnosis in allergic contact dermatitis is the patch test. This test has a sensitivity and specificity of between 70% and 80%15 (Quality of evidence II.ii) (Strength of recommendation A). Patch testing involves the reproduction under the patch tests of allergic contact dermatitis in an individual sensitized to a particular antigen(s). The standard method involves the appli- cation of antigen to the skin at standardized concentrations in an appropriate vehicle and under occlusion. The back is most commonly used principally for convenience because of the area available, although the limbs, in particular the outer upper arms, are also used. Various application systems are available of which the most commonly used are Finn cham- bers. With this system, the investigator adds the individual allergens to test discs that are loaded on to adhesive tape. Two preprepared series of patch tests are available – the TRUE (Pharmacia, Milton Keynes, U.K.) and the Epiquick (Hermal, Reinbek, Germany) tests. There are few comparative studies between the different systems. Preprepared tests are signifi- cantly more reliable than operator-prepared tests16–20 (Quality of evidence I). There is also some evidence that larger chambers may give more reproducible tests,21 but this may only apply � 2009 The Authors Journal Compilation � 2009 British Association of Dermatologists • British Journal of Dermatology 2009 160, pp946–954 Guidelines for management of contact dermatitis: update, J. Bourke et al. 947 to some allergens22 (Quality of evidence II.ii), and can be used to obtain a more definite positive reaction when a smaller cham- ber has previously given a doubtful one. The International Contact Dermatitis Research Group has laid down the stan- dardization of gradings, methods and nomenclature for patch testing.23 Timing of patch test readings The optimum timing of the patch test readings is probably day 2 and day 4.24 An additional reading at day 6 or 7 will pick up approximately 10% more positives that were negative at days 2 and 425 (Quality of evidence II.ii) (Strength of recommenda- tion A). The commonest allergens that may become positive after day 4 are neomycin, tixocortol pivalate and nickel. Relevance of positive reactions An assessment should be made of the relevance of each positive reaction to the patient’s presenting dermatitis. Unfortunately this is not always a simple task even with careful history taking and knowledge of the allergen’s likely sources and the patient’s occupation and ⁄or hobbies. Textbooks on contact dermatitis are an invaluable resource in this regard (Appendix 2). A sim- ple and pragmatic way of classifying clinical relevance of posi- tive allergic patch test reactions is: (i) current relevance – the patient has been exposed to allergen during the current episode of dermatitis and improves when the exposure ceases; (ii) past relevance – past episode of dermatitis from exposure to allergen; (iii) relevance not known – not sure if exposure is current or old; (iv) cross reaction – the positive test is due to cross-reaction with another allergen; and (v) exposed – a history of exposure but not resulting in dermatitis from that exposure, or no history of exposure but a definite positive allergic patch test. Patch test series The usual approach to patch testing is to have a screening ser- ies, which will pick up approximately 80% of allergens.26,27 Such series vary from country to country. There are two prin- cipal standard series, differing between the U.S.A. and Europe. Most dermatologists adapt these series by adding allergens that may be of local importance. The standard series should be revised on a regular basis. The North American Contact Der- matitis Group extended its standard series to a total of 49 allergens and the British Contact Dermatitis Society (BCDS) in 2001 expanded its series to include several common bases and preservatives (Appendix 3) and a number of other important allergens. There are six additions to the BCDS standard series. Following the emergence of new fragrance allergens, a new mix [Fragrance mix II: hydroxyisohexyl 3-cyclohexene car- boxaldehyde (Lyral), citral, farnesol, citronellol, alpha-hexyl- cinnamic aldehyde] has been tested and validated as a useful screening tool for fragrance allergy.28 The specific allergen Lyral is also tested separately because of the number of new cases of allergy reported.29 Compositae mix (2Æ5% pet.) has been recommended as it increases the rate of detecting Com- positae allergy.30 Disperse Blue mix, which contains the two commonest textile dye allergens Disperse Blue 106 and 124, has also been added to the standard series.31 More recently, propolis and sodium metabisulphite have also been added to the standard series. Five supplemental series have also been recommended. These series are outlined in Appendix 3. Sup- plemental series should be used to complement the standard series for particular body sites or types of agents to which the patient is exposed (Appendixes 3 and 4). The patient’s own cosmetics, toiletries and medicaments should be tested at non- irritant concentrations. This usually means ‘as is’ (undiluted product) for leave-on products and dilutions for wash-off products. Strong irritants such as powder detergents should not be patch tested. Occupational products should also be tested at nonirritant concentrations. The most useful reference source for documented test concentrations and vehicles of chemicals, groups of chemicals and products is that by De Groot.32 Guidelines for testing patients’ own materials can be found in the Handbook of Occupational Dermatology.33 However, false positives and false negatives often occur when patch test- ing products brought by the patient. Photopatch testing Where photoallergic dermatitis is suspected, photopatch test- ing may be carried out.34 Very briefly, the standard method of photopatch testing involves the application of the photo- allergen series and any suspected materials in duplicate on either side of the upper back. One side is irradiated with 5 J cm)2 of ultraviolet (UV) A after an interval (1 or 2 days) and readings are taken in parallel after a further 2 days. The exact intervals for irradiation and the dose of UVA given vary from centre to centre. The U.K. multicentre study into photo- patch testing has now been completed and published.35 It is recommended that allergens be subjected to 5 J cm)2 UVA and a reading taken after 2 days. The incidence of photoaller- gy in suspected cases was low at under 5%; however, further readings at 3 and 4 days increased the detection rate. The issue of whether to irradiate the test site after 1 or 2 days of allergen application was addressed in a separate study, which found in favour of a 2-day interval36 (Quality of evidence II.ii) (Strength of recommendation A). Open patch testing The open patch test is commonly used where potential irri- tants or sensitizers are being assessed. It is also useful in the investigation of contact urticaria and protein contact derma- titis. The open patch test is usually performed on the forearm but the upper outer arm or scapular areas may also be used. The site should be assessed at regular intervals for the first 30–60 min and a later reading should be carried out after 3–4 days. A repeated open application test, applying the sus- pect agent on to the forearm, is also useful in the assessment of cosmetics, where irritancy or combination effects may � 2009 The Authors Journal Compilation � 2009 British Association of Dermatologists • British Journal of Dermatology 2009 160, pp946–954 948 Guidelines for management of contact dermatitis: update, J. Bourke et al. interfere with standard patch testing. This usually involves ap- plication of the product twice daily for up to a week, stopping if a reaction develops. Preparation of the patient A number of factors may alter the accuracy of patch testing. Principal among these are the characteristics of the individual allergens and the method of patch testing. Some allergens are more likely to cause irritant reactions than others. These reac- tions may be difficult to interpret and are easily misclassified as positive reactions. Nickel, cobalt, potassium dichromate and carba mix are the most notable offenders in the standard ser- ies. As indicated above, preprepared patch tests are better stan- dardized in terms of the amount of allergen applied and are therefore more reproducible, but are prohibitively expensive in the U.K. Patient characteristics are also important. It is essential that the skin on the back is free from dermatitis and that skin dis- ease elsewhere is as well controlled as possible. This will help to avoid the ‘angry back syndrome’ with numerous false posi- tives.37 However, if a patient applies potent topical steroids to the back up to 2 days prior to the test being applied38–40 (Quality of evidence I), or is taking oral corticosteroids or immu- nosuppressant drugs, then there is a significant risk of false negative results. It has been claimed that patch testing is reli- able with doses of prednisolone up to 20 mg per day but that figure is based on poison ivy allergy, which causes strongly positive patch tests41 (Quality of evidence II.iii). The effect of sys- temic steroids on weaker reactions has not been assessed but clinical experience would suggest that if the daily dose is no higher than 10 mg prednisolone, suppression of positive patch tests is unlikely. UV radiation may also interfere with patch test results42 but the amount required to do so and the rele- vant interval between exposure and patch testing are poorly quantified (Quality of evidence II.iii). Testing for immediate (type I) hypersensitivity Although not strictly a part of assessment of contact dermatitis this is important particularly in the situation of hand derma- titis. Type I hypersensitivity to natural rubber latex (NRL) may complicate allergic, irritant or atopic hand dermatitis and may be seen in combination with delayed (type IV) hypersensitiv- ity to NRL or rubber additives. The two skin tests in common use are the prick test and the use test. Prick testing involves an intradermal puncture through a drop of NRL extract. A posi- tive reaction consists of an urticarial weal, which is usually apparent after 15 min, although it may take as long as 45 min to develop. A positive control test of histamine should be per- formed to check the patient does not give a false negative reaction from oral antihistamine ingestion. A negative control prick test with saline should also be performed to check if the patient is dermographic. The use test involves application of a glove that has been soaked for 20 min in water or saline. The prick test is generally favoured over the use test because of reports of anaphylaxis following the latter43 (Quality of evidence II.iii) (Strength of recommendation A). There are also occasional reports of anaphylaxis following prick testing with NRL extract.44 With the advent of standardized commercially avail- able NRL extracts this risk is probably greatly reduced. Some clinicians may prefer to perform a radioallergosorbent test (RAST) for NRL allergy, as they may not have adequate facili- ties or training to deal with anaphylaxis; however, the sensi- tivity and specificity may be less for RAST compared with prick testing. Skin prick and use tests are also useful when investigating protein contact dermatitis in occupations at risk such as chefs or veterinarians. Intervention and treatment Irritant contact dermatitis The management of irritant contact dermatitis principally involves the protecti