前田塾2019.12.28 入江

Vet Dermatol 2019; 30: 498–e149

DOI: 10.1111/vde.12793

The usefulness of short-course prednisolone during theinitial phase of an elimination diet trial in dogs withfood-induced atopic dermatitis
Claude Favrot*,†,1, Petra Bizikova†,1, Nina Fischer*, Ana Rostaher*

and Thierry Olivry†*Dermatology Unit, Clinical for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, 8057 Zurich,

Introduction
Switzerland†Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 1060 William Moore Dive, Raleigh, NC 27607,・皮膚食物有害反応(CAFRs)は、犬の皮膚病で一般的な疾患である。
USA・犬のCAFRsの原因は、非免疫性(食物不耐性)と免疫性(食物アレルギー)が含まれる。
Correspondence: Claude Favrot, Dermatology Unit, Clinical for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Winterthur・食物誘発性アトピー性皮膚炎(FIAD)は食物アレルギーの１つであり、食物アレルゲンがアトピー性皮膚炎(AD)の臨
erstrasse 260, 8057 Zurich, Switzerland. E-mail: cfavrot@vetclinics.uzh.ch
床的特徴である瘙痒性の皮膚疾患を引き起こすことである。
Background – Food allergy is a possible cause of atopic dermatitis (AD) in dogs; it is typically diagnosed follow・FIADと他のCAFRsの診断は、8〜10週間の食物除去試験(EDT)に基づいている。
ing an eight-week elimination diet trial (EDT) and a provocation with the original diet. This lengthy procedure is dif・長期EDTの問題点：偽陽性や偽陰性が出ることや、オーナーが積極的に持続させることができないこと。
ficult for owners and its interpretation may be unclear.
・目的：プレドニゾロンをEDT初期に使用することで、診断までの期間を短縮できるかを検証する。
Hypothesis/Objectives
Methods
and Materials – To test the effect of prednisolone used in the first weeks of an EDT in order to reduce
the total time period for diagnosis. The goal was to perform food challenges earlier than after the traditionally rec・症例：非季節性アトピー性皮膚炎の犬(組み入れ基準：表１)
ommended eight weeks.
・痒みの評価(図1, 表２)：PVAS10(1〜10)とオーナーによる主観的なグレード評価(1〜3)を毎週報告してもAnimals – Fifty-three dogs with AD were included in the study.
らう。

・EDTプロトコル(図2)Methods and materials – All dogs were fed a commercially available extensively hydrolyzed protein-based

commercial pet food and treated with prednisolone for at least two weeks to control pruritus and inflammation.
・食物負荷試験

Dogs were challenged two weeks after prednisolone finished, provided that no flare had occurred. Dogs with-EDT開始2週間前まで犬が食べていた市販のフードを、2週間続ける。
relapsing signs were fed the hydrolyzate for at least eight weeks with or without further prednisolone
treatment.
-痒み再発(PVAS>5、主観的なグレードが3)→負荷試験を中止し再度除去食へ→痒み改善(PVAS2、主観的なグレードが1)→FIADと診断。
Results – Ten of 53 dogs (19%) had no relapse after two weeks off prednisolone: they were subsequently chal-

Anallergenic/Ultamino

lenged with their regular food, had a relapse of signs and were diagnosed with a food-induced AD within four toResults(Royal Canin)
six weeks of starting the EDT. In the other dogs, signs remained uncontrolled without prednisolone or relapsed
・症例：53頭のAD犬が組み入れられた(表３)。
rapidly after its discontinuation: they were considered nonfood-allergic after an eight week EDT.
・10/53頭(19%)で食物負荷試験行える基準に合致し、食物負荷によりADが再発し、その後に再度除去食にすると臨床症状が改善した。→FIADと診断
Conclusion and clinical importance – This study demonstrates that a shorter EDT is possible if the allergic pru-

ritus and inflammation are initially controlled with a short course of glucocorticoids. This shortened trial is likely to-負荷してから症状の再発が出るまでの中央値は3日(範囲：1-10日)
improve owner adherence and facilitate the diagnosis of food allergy.
-FIADであった犬のEDTの期間は中央値28日(範囲：28-44日)

・43/53頭(81%)では、FIAD犬よりも長くEDTが実施され(中央値：60日、範囲：54-70日)、元の食事に戻しても臨床症状が悪CAFRs is based on a long eight to 10 week elimination
dietary trial (EDT).4 An evidence-based review suggested
Discussionthat an eight week EDT is needed to diagnose CAFR in
Cutaneous adverse food reactions (CAFRs) are a com・今回の研究では、グルココルチコイドで初期にでアレルギーによる痒みや炎症をコントロールしていれば、EDT期間の短縮(早>90% of dogs;5 eight weeks is frequently recommended
mon cause of skin diseases in dogs, even though theくて4週間で診断)が可能であることが示された。
prevalence varies greatly depending upon the populafor an EDT.5 Although the persistence of food allergens in
1
・EDT初期でのグルココルチコイドの使用がprospectiveに研究されたのは本研究が初めて。
the animal’s body in quantities sufficient to elicit clinicaltion. The pathogenesis of canine CAFRs currently issigns for up to two months would be difficult to explain
believed to involve both nonimmunological (i.e. food intol・プレドニゾロン未使用でも除去食に変更しただけで迅速な反応があったかもしれない。→未使用群との比較が必要であった。
immunologically, the chronicity of skin changes and selferances)
andimmunological(i.e.
foodallergies)
pro・犬の食事アレルギーが診断できない理由(＝長いEDTの期間をオーナーが積極的に維持できない)を解決できるが、EDTを進める2
perpetuating cutaneous inflammation seen in some dogs
cesses,thelatter
being
eitherIgEand/orcell-mediated.
にあたりオーナーとの密接なコミュニケーションが必要になる。
with chronic FIAD offers a logical rationale for the need ofFood-induced atopic dermatitis (FIAD) is the denomina・食物アレルギーの中でも、皮膚科学的症状以外の症状も同時に持つ犬での評価も必要。
such a lengthy period before achieving a noticeabletion currently proposed for one of the manifestations of批評improvement.
food allergies in which food allergens trigger a flare of a・コントロール群がないため、本当にプレドニゾロンで痒みスコアが減少しているかは分からない。
The interpretation of an EDT is based on the observapruritic skin disease that is clinically characteristic of ato・FIADと診断するには試験期間の短縮が可能であったが、否定するためには従来と同じ期間(8-10週間)が必要になっている。
tion of an improvement in skin lesions and pruritus during
pic dermatitis (AD).3 The diagnosis of FIAD and other
・他の除去食でも同様の結果が得られるか検証が必要。
the restrictive phase of this trial. To confirm the diagnosis,
this EDT should be followed by recurrence of signs following a challenge with the original diet.6,7 An important
Accepted 17 July 2019
1limitation in this is that dog owners are responsible for
Equal contribution.
Source of Funding: Royal Canin provided the food for free andobserving and reporting the signs of a positive challenge.
contributed to additional costs associated with the study followAlthough, in an experimental study involving research
up in both universities.
dogs with spontaneous food allergy, most dogs with IgEConflicts of Interest: Thierry Olivry is a scientific consultant formediated food allergy exhibited a flare of signs within
Royal Canin, Airmargues, France. The other authors have not
48 h after provocation with individual food items,8 the
化しなかった→nonfood-inducedAD(NFIAD)と診断
Introductionoften represented were Labrador retrievers (eight dogs),
French bulldogs (six) and West Highland white terriers(five); the median age at inclusion was three years (range:〈表１〉組み入れ基準1–10years). The median pruritus score at the time ofstarting the EDT was 6 (range: 3–10). Details on theenrolled subjects can be found in Table S1.

prednisolone in two dogs; in these, the duration ofRybníthe çek et al.
EDT was 43 and 44 days.
Altogether, 10 of 53 dogs (19%) met the proposed cri〈図１〉痒みの評価(PVAS10)
teria to be challenged with their original diet. These 10dogs exhibited a flare of AD after such provocation andclinical signs subsequently improved after reintroducing
the Anallergenic/Ultamino; these dogs were thus diagnosed as having a FIAD (Tables S2–S4); their median time
to flare after starting the food challenge was three days
(range: 1–10 days). In these food-allergic dogs, the median duration of the EDT was 28 days (range: 28–44 days).
The other 43 of 53 dogs (81%) underwent a longer EDT[median: 60 days (range: 54–70 days); Tables S2–S4]
without ever being assessed as having pruritus levels of
normal dogs off the prednisolone. In these dogs, clinicalsigns did not worsen after reintroduction of the former
diet and the diagnosis of nonfood-induced AD was therefore given.

Elimination diet trial
Per protocol, all dogs received at least one course of prednisolone during the initial phase of EDT, which lasted amedian of 14 days (range: 12–30 days; Table 1). After thisfirst prednisolone treatment phase, the pruritus was controlled in all dogs (i.e. PVAS10 ≤ 2). Eight of these 53 dogs
(15%) did not exhibit a flare of pruritus during the subsequent two weeks without receiving prednisolone.
In the other 45 dogs (85%), the median time to flare up
was eight days (range: 1–13 days; Table 1). Among these,
there were 12 of 45 dogs (27%) that remained on theAnallergenic/Ultamino diet for the entire eight week period of the EDT without ever reaching normal pruritus
Discussion〈表２〉痒みの評価(オーナーの主観的グレード)
levels.
The other 33 of 45 dogs (73%) received one or
two additional short courses of prednisolone and 31 had a
The failure to identify canine food allergies, whatever theirflare of signs when this glucocorticoid was discontinued.
manifestations, often results from poor owner adherence
By contrast, pruritus scores remained at normal levels
in maintaining the strictness of the recommended, yetduring the two weeks following the withdrawal oflengthy, eight to 10 week long EDT.5 The present study

Figure 1
the prurdescript
A had adown thnumberscale. Oor vers
ownersThis sca
ity of it
scratchior rubbi
starting
pen to pline thatcate thelevel of〈表３〉結果

Table 1. Summary of the study findings for dogs with food-induced and nonfood-induced atopic dermatitis (AD)

Number of dogs
Age [years; median (range)]
Sex (male:female ratio)
Pruritus score at the time of the 1st course of prednisolone
Duration of the 1st course of prednisolone [days; median (range)]
Number (%) of dogs having a flare of pruritus after the first prednisolone course
Time-to-flare of pruritus after stopping the induction course of prednisolone [days; median (range)]
Total duration of the elimination/provocation dietary trial [days; median (range)]
Time-to-flare of pruritus after the original food provocation [days; median (range)]500〈図２〉EDTプロトコル

Food-induced atopic
dermatitis AD

Nonfood-inducedAD

10
3 (1–7)3:7 = 0.4
6.1
14 (14–21)
2 (20%)
7 (7–8)28 (28–44)
3 (1–10)43
4 (1–10)
26:17 = 1.5
6.3
14 (12–30)
43 (100%)
10 (1–13)
60 (54–70)
NAJ. Rybníçek et al., Vet Dermatol, 2009

© 2019 ESVD and ACVD, Veterinary Dermatology, 30, 498–e149.

including healthy dogs (i.e. those presenting for prophylactic treatment
or vaccinations), dogs with non-cutaneous disease and dogs withskin conditions.

Evaluation of the canine pruritus severity scale
As the use of this scale involves two stages (the owner placing a markon the visual analogue scale followed by the mark being measured
with a transparent numerical scale), we first wanted to determine if
the process could be simplified into a single stage. In the first phase of
the study, two versions of the scale were therefore evaluated (Fig. 1).
The scales were essentially the same, but one version (the previously
reported pruritus severity scale) contained a standard visual analogue
scale (Fig. 1a), whereas the other version had the numerical markings
already printed onto it so that they were visible to the owner (Fig. 1b).
Both versions of the scale contained the same descriptors. Owners
were given either version A or version B of the scale, and theyscored before and after treatme
post-treatment responses.

Statistical analysis

Although the canine pruritus sev
data, the range of pruritus scores ga normal curve. Comparison of grou
non-parametric Mann–Whitney teAll analyses were performed usi
Windows (GraphPad Software, San

Results

Comparison of the numbe