原標(biāo)題：對(duì)狗過敏的診斷：謹(jǐn)防對(duì)狗的過敏
　　人類接觸皮毛類寵物的幾率較高，在歐洲，養(yǎng)狗比例從9%到34.8%等，而在美國(guó)30.4%的家庭養(yǎng)貓，36.5%的家庭養(yǎng)狗。然而，對(duì)狗過敏診斷是麻煩的。許多病人的自我報(bào)告通常是對(duì)過敏狀態(tài)的錯(cuò)誤歸類。與正規(guī)的過敏評(píng)估相比，單獨(dú)的確切的過敏病史在診斷中也并沒有什么優(yōu)勢(shì)，有27%的假陽性率。最近的研究中發(fā)現(xiàn)，對(duì)狗過敏原的皮膚點(diǎn)刺試驗(yàn)陽性應(yīng)答和與狗接觸后出現(xiàn)的癥狀之間有相關(guān)性。盡管明顯，但相關(guān)性并不是很大。因?yàn)殛栃灶A(yù)測(cè)值為80%時(shí)，風(fēng)團(tuán)直徑的cutoff值達(dá)10mm。另外，當(dāng)比較不同來源的皮膚點(diǎn)刺試驗(yàn)提取物時(shí)，發(fā)現(xiàn)對(duì)狗過敏的診斷受到提取物中過敏原含量的影響。
　　本研究比較了來自歐洲制造商的5種不同提取物。不同皮膚點(diǎn)刺試驗(yàn)提取物之間的蛋白含量存在20倍的差異，而不同廠家的提取物之間的過敏原Can f 1和 Can f 2含量差異大，5種提取物中有1種檢測(cè)不到Can f 1和 Can f 2。不同犬類過敏原Can f1、Can f2、Can f4、Can f6的鑒定(屬于lipocalin家族);犬血清白蛋白Can f 3;前列腺激肽釋放素Can f 5，這些已經(jīng)改善了對(duì)狗敏感病人的診斷方法。
　　最近鑒定的Can f 7（狗附睪分泌蛋白）的相關(guān)性還未知。Can f 1是主要的狗過敏原，能被50%到90%的對(duì)狗敏感的病人血清識(shí)別，lipocalins（細(xì)胞外蛋白家族）Can f 2和Can f 6及血清白蛋白Can f 3與其它皮毛動(dòng)物存在交叉反應(yīng)。單獨(dú)對(duì)Can f 5敏感已被認(rèn)為是對(duì)雄狗特異性過敏的標(biāo)志。應(yīng)用這一系列過敏原，能區(qū)分主要對(duì)狗敏感，主要對(duì)狗敏感和潛在的交叉反應(yīng)或與對(duì)其它動(dòng)物的過敏同時(shí)存在，或者主要對(duì)貓和馬過敏同時(shí)存在對(duì)狗的交叉敏感。目前尚不清楚犬類過敏原組份的致敏性是否與臨床相關(guān)。通過使用雙盲、安慰劑對(duì)照的食物挑戰(zhàn)，已經(jīng)表明IgE對(duì)花生過敏原組份如Ara h2和Ara h6，可能與兒童對(duì)花生敏感的全身反應(yīng)有關(guān)。這類研究尚未涉及吸入性過敏原。
　　本研究的目的是通過對(duì)60例(10-18歲)對(duì)犬類過敏的兒童進(jìn)行鼻腔激發(fā)試驗(yàn)，研究敏感程度與犬類過敏臨床癥狀之間的關(guān)系。他們發(fā)現(xiàn)陽性的鼻腔激發(fā)試驗(yàn)結(jié)果與對(duì)較多的狗過敏原組份敏感有關(guān)。lipocalins的致敏，尤其是Can f4和Can f6，與陽性的挑戰(zhàn)結(jié)果相關(guān)。Can f1特異性IgE的存在與陽性激發(fā)試驗(yàn)結(jié)果無關(guān)，可能是因?yàn)榇蠖鄶?shù)兒童對(duì)Can f1敏感。盡管如此，Can f1的臨床相關(guān)性通過Can f1特異性IgE水平增加與挑戰(zhàn)試驗(yàn)陽性結(jié)果之間的密切關(guān)系得到了證明。Can f3是最不常見的致敏成分，與陽性檢測(cè)結(jié)果無關(guān)。由于 Can f3 特異性IgE多見于對(duì)多種過敏原敏感的患者，因此狗血清白蛋白特異性IgE可能是一種更好的交叉反應(yīng)標(biāo)志物而不是臨床相關(guān)過敏標(biāo)志物。致敏譜之間的關(guān)系分析顯示，對(duì)所有蛋白組(即脂質(zhì)體、血清白蛋白和前列腺激肽酶)均敏感的患者鼻部刺激試驗(yàn)陽性結(jié)果的優(yōu)勢(shì)比最高[優(yōu)勢(shì)比，5.34;95% CI, 1.01-28.4])，而單獨(dú)對(duì)Can f5敏感與陰性挑戰(zhàn)結(jié)果相關(guān)。
　　使用鼻腔激發(fā)試驗(yàn)作為評(píng)估臨床對(duì)狗過敏的金標(biāo)準(zhǔn)。鼻腔激發(fā)試驗(yàn)在日常生活中并不經(jīng)常使用，但在研究中，尤其是在臨床試驗(yàn)中，它是一種有價(jià)值的工具。
　　本研究的一個(gè)局限性是，鼻腔挑戰(zhàn)的程序通常沒有很好的標(biāo)準(zhǔn)化。使用癥狀評(píng)分和/或鼻通暢度的客觀測(cè)量來評(píng)估鼻對(duì)過敏原的反應(yīng)性有多種方法，如鼻壓測(cè)量法、鼻聲測(cè)量法或鼻吸氣流量峰值法。然而，Kack等人使用的方法在不同類型的研究中使用過，最近發(fā)表的歐洲過敏和臨床免疫學(xué)學(xué)會(huì)(European Academy of Allergy and Clinical Immunology)關(guān)于鼻腔激發(fā)試驗(yàn)的主旨論文中，這一工具是否已被廣泛接受。
　　鼻腔激發(fā)試驗(yàn)的另一個(gè)缺點(diǎn)是皮膚測(cè)試的局限性(例如，過敏原含量的變化)可能也適用于用于激發(fā)的過敏原提取物。本研究使用的過敏原溶液具有良好的特征，提取液中檢測(cè)并顯示了所有相關(guān)的狗組份。最后，考慮到病史的不準(zhǔn)確性，激發(fā)試驗(yàn)可能是評(píng)估不同犬類過敏原致敏模式的最佳參考。
　　治療過敏性患者面臨的主要挑戰(zhàn)是區(qū)分無關(guān)的致敏和臨床過敏。如果病史與常規(guī)皮膚針刺試驗(yàn)或?qū)Υ痔嵛锏奶禺愋訧gE的聯(lián)合不能確定診斷，一個(gè)好的替代方法是使用暴露試驗(yàn)(鼻腔和結(jié)膜激發(fā)試驗(yàn)或口腔食物激發(fā)試驗(yàn))。雖然對(duì)病人來說，鼻腔和結(jié)膜的激發(fā)不比食物激發(fā)試驗(yàn)費(fèi)力和繁雜，但在日常生活中并不常用。除了標(biāo)準(zhǔn)化問題之外，缺乏國(guó)家監(jiān)管機(jī)構(gòu)注冊(cè)的挑戰(zhàn)性試驗(yàn)的致敏提取物可能會(huì)妨礙這些試驗(yàn)的應(yīng)用。過敏原組份的可用性為臨床醫(yī)生提供了更好地識(shí)別臨床相關(guān)敏感性的工具。對(duì)于兒童的食物過敏尤其如此，但是Kack et el7的研究表明在吸入物過敏的情況中也可以適用。分析過敏原組份IgE模式的作用可能因過敏原而異，但越來越多的研究支持在診斷過程中確定特定過敏原的IgE水平的附加值。盡管這項(xiàng)由Kack等人進(jìn)行的研究是IgE對(duì)犬類組份的致敏模式的確定，可能有助于識(shí)別真正的過敏反應(yīng)，但這并不意味著只有單一的標(biāo)志物可以檢測(cè)臨床相關(guān)性。通過鼻或結(jié)膜激發(fā)試驗(yàn)比較敏感性和特定組份的方法，對(duì)鑒別其他吸入物過敏患者的相關(guān)過敏原也有價(jià)值。根據(jù)可能的過敏原，分析過敏原組份的IgE模式可能有助于過敏的診斷。


延伸閱讀
JACI                                            
[IF:13.1]
Diagnosis of dog allergy: Beware of the dog
October 2018Volume 142, Issue 4, Pages 1058–1059
DOI：DOI: https://doi.org/10.1016/j.jaci.2018.08.006
Exposure to furred pets is high. In Europe dog ownership varies from 9.0% to 34.8%,1
whereas in the United States 30.4% of the households own cats and 36.5% own dogs.2
However, the diagnosis of dog allergy is troublesome. In general, self-reporting misclassifies allergic status in many patients. Even a structured allergy history alone is little better and results in false-positive rates for dog allergy of 27% compared with formal allergy assessment.
In a more recent study, it was found that skin prick test response positivity to dog was associated with a history of symptoms on exposure to dog.4
Although significant, the magnitude of the association was not high. For a positive predictive value of 80%, the wheal diameter cutoff amounted to 10 mm.
In addition, the diagnosis of dog allergy is hampered by varying levels of allergen content when comparing skin prick test extracts from different sources.5
In this study 5 extracts from European manufacturers were examined. Skin prick test extracts showed a 20-fold variation in protein content, whereas the dog allergens Can f 1 and Can f 2 varied widely between extracts, with undetectable levels in 1 of 5 extracts.
Identification of the distinct dog allergens Can f 1, Can f 2, Can f 4, and Can f 6 (belonging to the lipocalin family); the dog serum albumin Can f 3; and the prostatic kallikrein Can f 5 have improved the diagnostic approach for patients sensitized to dog.6
The relevance of the recently identified Can f 7 (dog epididymal secretory protein) is not known. Can f 1 is a major dog allergen recognized by 50% to 90% of patients sensitized to dog. The lipocalins Can f 2 and Can f 6 and the serum albumin Can f 3 are cross-reactive to other furred animals. Monosensitization to Can f 5 has been suggested as a marker for specific allergy to male dogs. Thus with this set of components, it is possible to discriminate between primary sensitization to dog, primary sensitization to dog and potentially cross-reactivity or cosensitization to another animal, or primary sensitization to cat or horse with cross-sensitization to dog.6
It is not always clear whether sensitization to dog allergen components points to clinical relevance. By using double-blind, placebo-controlled food challenges, it has been shown that IgE to peanut components, such as Ara h 2 and Ara h 6, can be associated with systemic reactions in children sensitized to peanut. Such studies have not been done with inhalant allergens.
aimed to study the association between sensitization and clinical symptoms of dog allergy as assessed by using nasal challenge testing in 60 children (age 10-18 years) sensitized to dog. They found that a positive nasal provocation test result was associated with sensitization to an increasing number of dog allergen components. Sensitization to lipocalins, in particular to Can f 4 and Can f 6, was related to a positive challenge result. The presence of IgE to Can f 1 was not associated with a positive provocation test result, possibly because the majority of children were sensitized to Can f 1. Nevertheless, the clinical relevance of Can f 1 was illustrated by a strong relationship between the increasing level of IgE to Can f 1 and a positive outcome on the challenge test. Can f 3 was the least common sensitizing component and not related to a positive test result. Because IgE to Can f 3 was mostly seen in multisensitized patients, IgE to dog serum albumin is perhaps a better marker for cross-reactivity than for clinically relevant allergy. Analysis of the relation between sensitization profiles showed that the highest odds ratio for a positive nasal provocation test result was found among patients who were sensitized to all protein groups (ie, lipocalins, serum albumin, and prostatic kallikrein [odds ratio, 5.34; 95% CI, 1.01-28.4]), whereas monosensitization to Can f 5 was associated with a negative challenge result.
used the nasal challenge test as the gold standard for assessing clinical allergy to dogs. Nasal provocation tests are not regularly used in daily practice, but they are a valuable tool in research, particularly in clinical trials.
A limitation of this study is that nasal challenge procedures are not well standardized in general. There are a variety of methods to assess nasal reactivity to allergens using symptom scores and/or objective measurements of nasal patency, such as rhinomanometry, acoustic rhinometry, or peak nasal inspiratory flow.8
However, the method used by K?ck et al7
has been used in different types of studies and is a well-accepted tool included in a recently published European Academy of Allergy and Clinical Immunology position paper on nasal provocation tests.8
Another drawback of the nasal challenge test is that the limitations of skin testing (ie, variability in allergen content) might also be true for allergenic extracts used for challenge. The allergen solution used in this study was well characterized, with all relevant dog components measured and present in the extract. Finally, taking the inaccuracy of the history into account,3
the challenge test might be the best available reference for evaluating sensitization patterns to different dog allergens.
The major challenge in managing allergic patients is always to differentiate between irrelevant sensitization and clinical allergy. If the combination of a history with conventional skin prick tests or specific IgE to the crude extract is insufficient to establish the diagnosis, a good alternative is use of exposure tests (nasal and conjunctival provocation tests or oral food challenges). Although less laborious and less burdensome for patients than food challenge tests, nasal and conjunctival provocations are not commonly used in daily practice. Apart from standardization issues, lack of allergenic extracts for challenge tests that are registered by national regulators might hamper use of these tests. The availability of allergen components has provided the clinician with tools to better identify clinically relevant sensitizations. This is particularly true for food allergy in children, but the study by K?ck et el7 shows that this can also be the case in the setting of inhalant allergy. The effect of analyzing IgE patterns to allergen components might vary per allergen, but an increasing number of studies underwrite the added value of determining levels of IgE to specific allergens in the diagnostic process. Although the study by K?ck et al7 does not point to a single marker to detect clinical relevance, determination of the pattern of IgE sensitization to dog components might be helpful in recognizing true allergy. The approach of comparing sensitization to specific components with nasal or conjunctival challenge tests could also be valuable to identify the relevant allergens for patients with other inhalant allergies. Depending on the suspected allergens, analysis of IgE patterns to allergen components may be helpful in the diagnosis of allergy (Fig 1).
Author：
MD, PhD Roy Gerth van Wijk
　　創(chuàng)建過敏性疾病的科研、科普知識(shí)交流平臺(tái)，為過敏患者提供專業(yè)診斷、治療、預(yù)防的共享平臺(tái)。