兽医师猫传染病专题等多个文件-015esavs-猫病ii1猫口炎feline stomatitis katrin

Katrin

HartmannProf.,

Dr.

med.

vet.,

Dr.

habil.,

Dipl.

ECVIM-CAFeline

Stomatitis猫的口炎„Mister

Q“Siamese

暹罗猫9

years

9岁male

neutered雄性已绝育lives

in

Munich住在慕尼黑single-cat

household,only

indoors独养，室内referred

for

stomatitis因口炎转诊FIV

infection

known

since

6

years

6年前查出

FIVbiopsy:

lymphoplasmocytic

stomatitis活检：淋巴浆细胞性口炎„Mister

Q“Stomatitis口炎=

inflammation

ofthe

mucous

membranes

of

themouth=口腔黏膜的炎症very

common很常见often

young

cats常见于青年猫often

chronic通常是慢性的often

without通常没有牙stomatogingivitis,

gingivostomatitis,faucitis，lymphoplasmocytic

stomatitis口腔牙龈炎，龈口炎，咽喉炎淋巴浆细胞性口炎Etiology

病因primary

pathogenes?oral

microbial

flora/病原体？?口腔菌群/牙chronic timulation?抗原慢性刺激immune-mediated

processes?免疫介导过程immune

dysregulation?免疫失调Etiology病因histology

组织学:mainly

plasma

cells

and

lymphocyteswith

possible

neutrophilic

and

eosinophilicinflammation

(different

degrees)主要是浆细胞和淋巴细胞性炎症，可能有中性粒细胞和嗜酸性粒细胞性炎症（不同程度）circulating

lymphocytes

外周淋巴细胞⇧expression

von

inflammatory

cytokines炎性细胞因子表达增高=>

chronic timulation

and/ordysregulation

of

the

immune

system慢性抗原刺激和/或免疫系统调节异常Potential

Pathogenes

Involved潜在的病原体feline

calici猫杯状

feline

herpes猫疱疹(FCV)(FHV)feline

immunodeficiency猫免疫缺陷(FIV)felines

leukemia

(FeLV)猫白血病Bartonella

(mainly

Bartonella

henselae)氏体（主要是汉氏氏体）other

bacteria

(e.g.,Bacteroides

spp.)其它细菌如，拟杆菌属）Study:

Relevance

of

Pathogenes研究：相关病原体52

cats

with

chronic

stomatitis

52只慢性口炎猫stomatitis>3

weeks

口炎>3周no没有牙or

other

dental

changes或其它口腔病变50

age-matched

control

cats50只

一致的对照猫clinically

healthy

临床健康no

history

ofstomatitis

无口炎病史examinations

检查生化history,

incl.

accurate

vaccination

history病史，包括精确的免疫史physical

examination

体检blood

tests

血检CBC

and

serum

biochemistry

血常规和antibodies

(FIV,

FCV,

Bartonella

henselae),汉氏巴）氏体)抗体检测（猫免疫缺陷 ,

猫杯状尔通氏体）(FeLV)

抗原检测

（猫白血病RNA/DNA(Bartonella

henselae汉氏swabs

oftheoral

口腔拭子RNA/DNA

(FCV,

FHV,

Bartonella

henselae)Study:

Relevance

of

Pathogenes研究：相关病原体stomatitis口炎组

n=52controls对照组

n=50p*标准差FCV

swab

FCV拭子53.8

%14.0

%<

0.001FCV

AB

FCV抗体78.8%58.0

%0.024FHV

swab

FHV拭子13.5%6.0%0.320FIV

blood

FIV血液5.8%0

%0.121FeLV

blood

FeLV血9.6%0

%0.060B.

henselae

swab汉氏 氏体拭子19.2%12.0

%0.320B.

henselae

blood汉氏 氏体血液17.3%8.0%0.161B.

henselae

AB汉氏 氏体抗体9.6

%10.0

%1.000*Chi-square/‘s

exact

testStudy:

Relevance

of

Pathogenes研究：相关病原体stomatitis口炎组n

=

52controls对照组n

=

50p*标准差FCV

swab

FCV拭子53.8

%14.0

%<

0.001FCV

AB

FCV抗体78.8

%58.0

%0.024FHV

swab

FHV拭子13.5

%6.0%0.320FIV

blood

FIV血液5.8

%0

%0.121FeLV

blood

FeLV血9.6

%0

%0.060B.

henselae

swab汉氏 氏体拭子19.2

%12.0

%0.320B.

henselae

blood汉氏 氏体血液17.3

%8.0%0.161B.henselae

AB汉氏 氏体抗体9.6

%10.0

%1.000*Chi-square/‘s

exact

testStudy:

Relevance

of

Pathogenes研究：相关病原体stomatitis口炎组n

=

52controls对照组n

=

50p*标准差FCV

swab

FCV拭子53.8

%14.0%<0,001ODDs

ratio比值比（OR）confidence

interval置信区间7,12.5

<

OR

<

21.3FCV

AB

FCV抗体78.8

%58.0%0,024ODDs

ratio比值比confidence

interval置信区间2,71.0

<

OR

<

7.1*Chi-square/‘s

exact

testStudy:

Relevance

of

Pathogenes研究：相关病原体stomatitis口炎组n

=

52controls

对照组n

=

50p*标准差roam

outside

流浪猫42,3

%56,0

%0,173multi-cat

househ.家里饲养多只猫56,3

%63,4

%0,491%male

%雄性59,6

%58,0

%0,870%DSH

%本地短毛猫78,8

%92,0

%0,063vaccination

免疫48,1

%44,0

%0,784agemedian

中值mean

平均值5,0

years6,0

years5,0

years6,1

years0,911*Chi-square/‘s

exact

testStudy:

Relevance

of

Pathogenes研究：相关病原体Potential

Pathogenes

Involved潜在的相关病原体pfeline

calicifeline

herpes(FCV)

猫杯状

（FCV）(FHV)

猫疱疹feline

immunodeficiency

(FIV)猫免疫缺陷felines

leukemia (FeLV)猫白血病Bartonella

(mainly

Bartonella

henselae)氏体（主要是汉氏

氏体）other

bacteria

(e.g.,

Bacteroides

s其它细菌（如，拟杆菌属）Feline

Calici猫杯状(FCV)(FCV)Etiology

病因

Symptoms

症状

DiagnosisTreatment

治疗

Prophylaxis

预防Feline

Calici猫杯状(FCV)(FCV)Etiology

病因

Symptoms

症状

DiagnosisTreatment

治疗

Prophylaxis

预防Feline

Calici猫杯状(FCV)(FCV)Etiology

病因clinical

signs

临床症状DiagnosisTreatment

治疗

Prophylaxis

预防Feline

Calici猫杯状(FCV)(FCV)small,

unenveloped

RNA-with

cup-like

impressions小的，似杯状的无衣壳RNAhighly

contagious

传染性强infectious

up

to

3

weeks

in

the

environment在环境中3周仍有

性high

variability=>变异性强strains

with

high

pathogenicity

高致病性菌株ABCDEORF

15’3’ORF

35’HVRCons3’HVRFelineCalici猫杯状(FCV)(FCV)ORF

2Excretion

排毒TransmissionTenacity稳定性carrier

state带毒状态下by

oral

and

nasal

discharge,

saliva(few

days

up

to

life-long

period)从口腔和鼻

物，唾液（几天到

）generally

direct,通常直接indirect

transmission

possible可能发生间接relatively

stable

in

theenvironment在环境中相对稳定（可达3周）(up

to

3

weeks)replication

in

tonsills

andlymphoepithelial

tissuecontinuous

shedding在扁桃体和淋巴上皮组织中

不断脱壳FCV

–

Epidemiology猫杯状

-流行病学Carrierstatus

FCV猫杯状

带毒状态elimination排毒chronic

shedder

慢性脱壳+susceptible

cat疑似病例40%colony

cats

40%群居猫

25%show

cats

25%纯种猫

8%household

pets

8%家养猫

20%practice

cases

实践案例cat

with

acute

FCV

infection急性FCV

的猫chronicSequelae慢性后遗症clinicalRecovery临床康复许many

cats

stillshedding30days

after

infection多猫30天后仍然排毒50%

cats

still

shedding75

days

post

infection50%的猫

后75天仍然排毒eliminatednon-carriers排毒后成为非携带者self-limiting自限性的or

life-long带毒Carriers携带者Gaskell

&

Bennett,1996FCV

-carrierstateFeline

Calici猫杯状(FCV)(FCV)Etiology

病因clinical

signs

临床症状DiagnosisTreatment

治疗

Prophylaxis

预防incubation

period潜伏期Signs

症状Nose

鼻Eyes

眼oral

口腔respiratory

tract呼吸道chronic

infections慢

染有时打喷嚏，

物+2-4

days

2-4天generally

milder

than

with

FHV通常比同时

FHV要轻sometimes

sneezing,

discharge

+usually

no

ocular

signs

通常没有眼部症状big

vesicles,ulcers

大水泡，溃疡rarely

p onia

罕见chronic

proliferative

stomatitis慢性增生性口炎Clinical

Signs临床症状Clinical

Signs临床症状Clinical

Signs临床症状

/cpdvets/LimKitten

Syndrome

Pedersen

et

al.,

1983幼猫跛行综合征Lmainly

in

kittens

of

6

-

12weeks主要在6-12周的幼猫Loften

after

vaccinations

常在免疫之后Lusually

intermittent,

often

with

fever一般是间歇性的，常伴发热Lmostly

self-limiting

大多数是自限性的Lcertain

antigenic

variant?

确定有抗原变异？Lrelated

to

vaccine?免疫相关？L replication

in

joints?在关节吗Limmune-mediated?免疫介导的？Lincreased

in

1-acid

glycoprotein?

-酸性糖蛋白升高Chronic

Proliferative

Stomatitis慢性增生性口炎Lchronic

慢性Lrecurrent

复发Lproliferative

增生Lulcerative

溃疡Llymphocytic/plasmocytic淋巴细胞/浆细胞Limmune-mediated

reaction

to

chronicFCV

infection慢性FCV

的免疫介导效应Lrole

of

chronic

carriers?慢性携带Lrole

of

FIV

and

FeLV?猫免疫缺陷者的作用和猫白血病

的作用in

some

studies

75

%

of

cases

of

chronic

stomatitis在某些研究结果中慢性口炎病例的75%hemorrhagic

syndrome(generalized

systemic

calicisyndrome)性综合征（系统性杯状

综合征）Pedersen

et

al.,2000recently

described

syndrome最近此综合征有被描述severe

„systemic

hemorrhagic

fever”严重的“系统性

热”high

mortality,

mainly

older

cats率高，主要发生于老年猫no

protection

by

common

vaccines没有常规 保护GSCVS系统性杯状

综合征LDSH

本地短毛猫L3

years

old

3岁Lmale

neutered

绝育公猫L

single

cat

household,

indoor

only家里只养了一只，室内Lregularly

vaccinated,常规免疫complete

primo-vaccination,首次免疫完全last

vaccination

(HCP)最后一次免疫（猫三联）4months

ago4个月前“Moritz”“Moritz”History

病史Lsince

1

day

problems

to

urinate

1天前排尿有问题

L

stranguria

痛性尿淋漓Ltoday

anorectic

今天开始厌食physical

examination

体检Llarge

and

tense

bladder大且紧张DiagnosisFLUTD

猫下泌综合征“Moritz”Treatment

治疗Lindwelling

catheter

内置导尿管Lemptying

ofthe

bladder排空Lfluid

therapy

(incl.

electrolyte

replacement)输液治疗（包括，补充电解质）Lpain

medication

止痛药follow-up

回访L ng

better

shortlyafter

treatment治疗后很快好转

Lstarted

eating

开始进食

Lcatheter

left

in

placefor

24

hours导尿管留置24小时“Moritz”the

next

day

…第二天...“Moritz”物物new

problems

新问题Lfever

发热Locular

discharge

眼Lnasal

discharge

鼻Lsneezing

喷嚏Lulcerations

on

the

tongue舌溃疡Lulcerations

on

the

paws爪子上溃疡„Moritz“Foto:

S.Unterer,

München„Moritz“Foto:

S.Unterer,

München“Tiger”“Bä24

Hours

Later24小时之后“Tiger”“Moritz”†††“Bärli”72

Hours

Later

…72小时后Feline

Calici猫杯状(FCV)(FCV)Etiology

病因clinical

signs

临床症状DiagnosisTreatment

治疗

Prophylaxis

预防FCV

–

DiagnosisFCV-detection

of

antibodies抗体检测-

PCR聚合酶链反应detection

of

检测- isolation

(cell

culture)分离（细胞培养）not

useful

无效vaccination

免疫antigenic

variability抗原变异性sensitive

and

specific敏感且特异Specific

特异

sensitive?敏感？strain

differentiation亚型鉴别Feline

Calici猫杯状(FCV)(FCV)Etiology

病因clinical

signs

临床症状DiagnosisTreatment

治疗

Prophylaxis

预防Supportive

Treatment支持疗法fluid

therapy

输液治疗=>Rehydration

再水合(=>

amelioration

of

the

mukociliary

clearance)（改善粘液纤毛清除率）gesia

if

necessary需要时进行镇痛Lvitamin

A维生素ALvitamin

C维生素CLvitamin

B

complex复合维生素B5000

IU/kg

PO

q

24

h5000IU/kg

口服每24h一次80

mg/kg

PO

q

8

h80mg/kg

口服每8h一次SC

q

48

h皮下每48h一次Supportive

Treatment支持疗法vitamins

(mucosal

regeneration)维生素（黏膜再生）Supportive

Treatment支持疗法nutritional

management

营养管理purée

and

warmed

food(microwave)果泥和热水（微波）appetite

stimulation

刺激食欲diazepam

(Valium®)

0.05

-

0.25

mg/kg

IV(immediate

effect)

0.05-0.25mg/kg

静注（即时效应）cyproheptadin

(Peritol®)

0.5

-

1

mg/kg

q

12

h

PO赛庚啶(Peritol

®)0.5-1mg/kg每12小时一次口服mirtazapine

3

mg/cat

PO

米氮平3mg/猫口服tube

feeding

if

necessary必要时可用饲喂管喂食Nasal

Tube鼻饲管Esophagal

Tube食道饲喂管effective

invitro体外作用controlledstudy

in

vivo体内对照组effective

invivo体内作用assessment

of

effectiveness(1

–

4)效果评估Immunglobulins免疫球蛋白Yes

有No

无Unknown未知possibly

effective

(4)有效率（4）Ribavirin

利巴韦林Yes

有jaNo

无too

toxic

systemically

(2),全身毒性强（2）possibly

as

aerosol(4)气雾剂有效率（4）humaninterferon-α人用α-干扰素s.c.

high

dose皮下高剂量p.o.

low

dose口服低剂量Yes

有No

无Unknown未知Unknown未知possibly

effective

(4)有效率（4）Yes

有No

无probably

not

effective

(4)无效率（4）felineinterferon-ω猫ω-干扰素Yes

有No

无Unknown未知possibly

effective

(3)有效率（3）Antiviral

Chemotherapy抗

化疗effective

invitro体外作用controlledstudy

in

vivo体内对照组effective

invivo体内作用assessment

of

effectiveness(1

–

4)效果评估Immunglobulins免疫球蛋白Yes

有No

无Unknown未知possibly

effective

(4)有效率（4）Ribavirin

利巴韦林Yes

有jaNo

无too

toxic

systemically

(2),全身毒性强（2）possibly

as

aerosol(4)气雾剂有效率（4）humaninterferon-α人用α-干扰素s.c.

high

dose皮下高剂量p.o.

low

dose口服低剂量Yes

有No

无Unknown未知Unknown未知possibly

effective

(4)有效率（4）Yes

有No

无probably

not

effective

(4)无效率（4）felineinterferon-ω猫ω-干扰素Yes

有No

无Unknown未知possibly

effective

(3)有效率（3）Antiviral

Chemotherapy抗

化疗Ribavirin利巴韦林commercially

available

e.g.

Ribazole®有商品化药物，如Ribazole®antiviral

effects

抗

nucleoside效果ogue

(guanosine

derivative)核苷类似物（鸟苷衍生物）

interferes

with

DNA

and

mRNA

synthesis干扰DNA和mRNA的Dosage

剂量

11

mg/kg

q

24

h

PO

or

IV

(max.

7

days)11mg/kg

24h一 次

口服或静注（最长7天）

only

in

combination

with

interferon-

orinliposomes?只能与a/w-干扰素或脂质联合使用side

effects

(already

in

therapeutic

dosage!)副作用（已经在治疗剂量中出现）

myelosuppression,

hepatotoxicity骨髓抑制，肝毒性

diarrhea,

gastro-intestinal

ulcera腹泻，胃肠道溃疡Ribavirin:

Experimental

Study

(2)利巴韦林：实验报告(2)ribavirin

(25

mg/kg

q

8

h

PO

for

10

days)利巴韦林（25mg/kg

每8h一次口服服用10天）1

day

or

4

days

after

exposition

(aerosol)

to

FCV在FCV中1到4天后（气雾剂）=>clinical

signsmore

severe

临床症状更严重=>severe

side

effects

副作用越剧烈Povey,

1978Immunglobulins免疫球蛋白commercially

available

in

Europe

(Feliserin®)在欧洲有商品化药物(Feliserin®)antiviral

effects

effect

against

FCV?抗作用

抗FCV的效果neutralizing

antibodiesagainst

FCV,

FHV,

FPV中和FCV,FHC,FPV抗体Dosage

剂量

for

prophylaxis

1

injection

SC

(1

ml)皮下注射1次（1ml）预防

for

treatment

3

injektionen

SC

(1

ml)

q

24

hlokal

application?治疗每24h一次皮下注射3支外用？side

effects

副作用

anaphylaktic

reaction

in

cats

(repeated

application)猫的过敏反应（重复应用时）human

interferon-,

feline

interferon-人用a-干扰素，猫w-干扰素antiviral

effects

抗

作用

inhibits抑制assemly

and

budding装配和芽孢

cytokine,

immunomodulatory

effect细胞因子，免疫调节作用Dosage

剂量

huIFN-

high

dose

105

IU/kg

q

24

h

SQ

(short

term)人a-干扰素高剂量105

IU/kg

每24h

皮下（短期）

huIFN-

low

dose

1

(-50)

IU

q

24

h

PO

(long

term)人a-干扰素低剂量1(-50)IU

每24h

口服（长期）

feIFN-

106

IU/kg

S 24

h

on

5

consecutive

days猫w-干扰素

106

IU/kg

皮下每24h

连用5天side

effects

副作用

rarely

allergic

reactions

(huIFN-)少见过敏反应（人a-干扰素）Interferon-ωΩ-干扰素Interferon-ωΩ-干扰素L

in

vitro

strain-dependent

efficacyTaira

et

al.,

2005,

Kyoko

et

al.,2008品种依赖型体外有效性no

controlled

clinical

studies没有对照的临床研究----multi-center

study

多中心研究no

FCV

diagnostics

没有

FCVno

controls

没有对照not

controlled,

all

cats

received

symptomatic

treatment所有猫接受对症治疗felines

interferon-ω

2.5

or

5

x

106

IU/kg

IV

q

24

h

for

3

daysimprovement

<

4

days

after

signs

had

appeared猫ω-干扰素

2.5

or

5

x

106

IU/kg

静注每24h一次

3天出现临床症状后4天之内得到改善efficacy?有效？Interferon-ω

in

Acute

FCV

InfectionΩ-干扰素在急性FCV

中的应用field

study(Japan)领域研究（Uhino

et

al.,

1997160

cats

with

URTD

or

stomatitis160只猫，上呼吸道疾病或口炎）Experimental

Drugs实验性药物-specific

antiviral

抗特异

药物phosphorodiamidate

morpholino

oligomer磷酰二胺吗啉代低聚物experimental

infection

实验

染=>improved

survival

rate

提高存活率Smith

et

al.,

2008not

commercially

available

没有商品化药物Treatment

of

Chronic

Stomatitis慢性口炎的治疗Interferon-ω

in

Chronic

Stomatitisω-干扰素在慢性口炎中的应用lokale

treatment

with

interferon-Mihaljevic,

2003局部使用-干扰素sofar

no

placebo-controlled

studies(!)至今没有可靠的对照研究feline

interferon-

2.5

x

106

IU/kginjection

of

several

depots

of

0.1

ml

(gingiva)

+

left

over

SQ猫w-干扰素2.5x106

IU/kg

0.1ml多点注射（牙龈）+剩余皮下treatment

repeated

if

necessary

必要时重复important:

proper

dental

surgeries

(!)重要的是：恰当的牙科手术efficacy

of

interferon-ω???ω-干扰素有效性？？？Treatment

of

Chronic

Stomatitis慢性口炎的治疗prednisolone0,5

mg/kg

q

12

h

PO龙0.5mg/kg

每12h一次口服+cyclosporin

环孢菌素week

5

10

mg/kg

q

24

h

PO

for

5

days,

2-day

break,afterwards

5

mg/kg

q

12

h

PO

for

5

days,

2-day

break,after

that

5

mg/kg

q

12

h

PO

for

5

days,

2-day

break,etc.5周10mg/kg

每24h一次口服5天，停2天，之后5mg/kg

每12h一次口服5天，停2天，之后5mg/kg

每12h一次口服5天，停2天…Alternative

可选择tooth

extraction

拔牙if

necessary

all

teeth!必要拔掉所有牙齿Treatment

of

Chronic

Stomatitis慢性口炎的治疗Feline

Calici猫杯状(FCV)(FCV)Etiology

病因clinical

signs

临床症状DiagnosisTreatment

治疗

Prophylaxis

预防Problems

with

Vaccination免疫带来的问题no

complete

protection

against

disease对疾病没有完全的保护性L only

against

developm