Professional Documents
Culture Documents
Abstract The objectives of this study were to characterize the role of intermittent vs. continual ea exposure
in the development of ea allergy dermatitis (FAD) in cats, assess the accuracy of intradermal skin testing
(IDST) and in vitro testing, and document the incidence and histopathological features of indolent lip ulcers.
Ten ea-naive cats were divided into two groups. One group received intermittent ea exposure for 120 days.
Thereafter, both groups of cats received continuous ea exposure for 120 days. In vitro testing for ea salivary
antibody and IDST utilizing both whole ea antigen and ea salivary antigen were performed. Eight of 10 cats
developed clinical signs of FAD within 3 months and ve of these eight cats developed lip ulcers which where
characterized histopathologically by ulceration with predominantly neutrophilic inammation and surface
bacterial colonization. There was no association between the presence or absence of clinical signs and positive
IDST or in vitro results, and no dierence in the development of clinical signs was noted between the two
groups of cats.
Keywords: feline, ea exposure, ea allergy dermatitis, intradermal skin test, in vitro test, indolent lip ulcers.
INTRODUCTION
Although ea allergy dermatitis (FAD) is the most
common allergic skin disease of cats, little is known
regarding the immunopathogenesis of ea allergy in
this species.1,2 Contrary to what occurs in dogs,
anecdotal observations suggest that intermittent ea
exposure in cats may play a protective role against
the development of FAD.
A clinical diagnosis of feline FAD is frequently
made based on clinical signs and response to ea
control.3 In addition, intradermal skin testing (IDST)
has been utilized as an aid in the diagnosis of FAD,
with a positive predictive value of 85100%.36 The
use of in vitro testing has been controversial due to
the relatively low positive predictive values for feline
FAD.2,4 However, due to recent advances in assay
technology, in vitro testing may be a better predictor
of clinical disease in cats than IDST.7
Clinical signs in cats with FAD are quite variable
and include miliary dermatitis, self-inicted alopecia
Correspondence: Sarah Colombini, DVM, DACVD, Gulf Coast
Veterinary Dermatology & Allergy, 1111 West Loop South, Suite
120, Houston, Texas 77027, USA.
Funded by a grant from the American College of Veterinary
Dermatology and Louisiana State University Department of
Veterinary Clinical Sciences, ELISA testing and ea salivary
antigens for intradermal skin testing were provided by Heska Corp.
# 2001 Blackwell Science Ltd
and lesions associated with the eosinophilic granuloma complex (indolent lip ulcer, eosinophilic plaque,
eosinophilic granuloma).1,2 Indolent lip ulcers are the
most common of the dermatoses included in the
eosinophilic granuloma complex and present as
proliferative, ulcerated lesions which typically occur
unilaterally or bilaterally on the upper lip adjacent to
the upper canine tooth.812 Little research has been
done regarding the etiopathogenesis of these dermatoses since they were rst described over 35 years
ago.8,9 Proposed causes of indolent lip ulcers include
genetic, viral, psychogenic, traumatic, immunemediated, bacterial and allergic diseases.8,1113 As is
evident from this long list of proposed aetiologies, the
underlying cause(s) of these lesions remains obscure.
A high incidence of indolent ulcers was noted in a
group of related specic pathogen free (SPF) research
cats, suggesting a possible genetic basis.8 In addition,
one of the authors (CSF) has worked with cats from
this colony in a variety of experiments. During this
time it was noted that the induction of ea allergy in
this group of ea-naive cats resulted in a remarkably
high incidence (8/14) of indolent lip ulcers, the onset
of which coincided with skin test or ELISA-positive
conversion. In both groups of cats, the lesions
typically appeared around one year of age, and
would wax and wane. Controversy also exists in the
literature regarding the histopathological features of
acute indolent lip ulcers.2,8,11,14,15
155
243 DISC
156
S. Colombini et al.
experimental group every 2 weeks during the 120day intermittent ea exposure period to document the
time of positive seroconversion. Thereafter, both
groups of cats were subjected to continuous ea
exposure for 120 days. Fifty free-roaming eas were
applied to each of the ten cats twice weekly. In vitro
tests were performed on both groups of cats every 2
weeks during the 120-day continuous ea exposure
period. The endpoint of 120 days was chosen based
on previous observations of one of the authors (CSF)
that most cats become ea allergic between 100 and
120 days. Intradermal skin tests were performed on
all cats at the beginning of continuous ea exposure
(120 days) and end (240 days) of the study.
All cats were examined weekly for development of
dermatologic lesions (i.e. miliary dermatitis, selfinicted alopecia, linear granulomas, etc.). The lesions
were scored subjectively by the principle author (SC)
on a scale of 03, with 0 corresponding to no clinical
signs, 1 corresponding to mild clinical signs (i.e. mild
alopecia with no dermatitis, aecting 530% of the
body), 2 corresponding to moderate clinical signs (i.e.
moderate alopecia, miliary dermatitis, etc., aecting
3060% of the body) and 3 corresponding to severe
clinical signs (severe alopecia, miliary dermatitis,
excoriations, etc., aecting 460% of the body).
Occurrence of indolent lip ulcers was documented
and the lesions were biopsied as soon as evident using
either a 6-mm punch biopsy instrument or #11 scalpel
blade. Telazol (tiletamine/zolazepam, 0.10.3 mL, IM)
and local subcutaneous lidocaine (0.10.3 mL per site)
were employed for anaesthesia and analgesia. The
biopsy specimens were xed in 10% buered formalin
for histopathologic evaluation. All specimens were
examined by the same pathologist (ECH).
Statistics
All data was evaluated using categorical methods. In
vitro titres 5100 were considered positive, while titres
5 100 were considered negative. Intradermal skin test
scores were categorized on a scale of 04. Clinical signs
were categorized on a scale of 03, with 0 = no clinical
signs, 1 = mild clinical signs, 2 = moderate clinical
signs, and 3 = severe clinical signs. The data was
analysed using Mantel-Haenszel methods for repeated
categorical data, specically looking for associations
between in vitro titres, IDST scores and clinical signs.17
In addition, comparison of these associations between
the two groups of cats was performed. These methods
accounted for repeated measurements on cats over
time. PROC FREQ (SAS version 6.12, SAS Institute,
Cary, NC, USA) was used for all analyses.
RESULTS
All ten cats were negative on the initial intradermal
skin test and lacked dermatologic lesions at the start of
the study. Two of the ten cats initially had positive ea
salivary antibody titres on in vitro testing [Table 1].
243 DISC
Feline ea allergy and lip ulcers
157
day
0
day
14
day
28
day
42
day
56
day
70
day
84
day
98
day
112
day
120
day
134
day
148
day
162
1
2
3{
4
5{
6{
7{
8
9{
10
0
0
1
1120
0
0
1
150
0
0
1
0
0
2
0
20
0
0
1
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
3
2
0
0
61
0
0
7
0
45
2
0
32
4
443
7
26
3
33
35
9
4
0
38 1781
0
26
8
17
83 454
1924 4200
11
42
18
27
day
176
day
190
day
204
day
218
61
34
4
1517
29
62
425
4029
74
22
267 397
838
12
28
13
6
2
3
3093 3665 3034
8
8
20
31
39
200 203
135
4200 4200 4200
71
42
12
15
14
0
day
232
day
240
1579
16
1
2840
9
43
138
4200
14
16
1909
625
0
3443
1
4
82
4200
7
11
Lip
ulcers
Intermittent
ea exposure
Clinical
sign score*
IDST score
day 120{
Flea
FSAg
15
30
15
30
IDST score
day 240{
Flea
FSAg
15
30
15
30
In vitro
titres
1
2
3
4
5
6
7
8
9
10
No
No
Yes
Yes
Yes
No
Yes
No
Yes
No
No
No
Yes
No
Yes
Yes
Yes
No
Yes
No
2
0
1
2
1
1
3
1
2
0
0
0
1
0
0
1
0
0
0
0
3
3
1
2
1
1
2
2
2
2
+
+
+
+
0
0
0
0
0
2
2
0
1
0
0
0
3
0
1
2
3
0
1
0
0
0
1
0
0
0
2
0
1
0
3
3
0
2
0
1
1
0
1
1
3
2
0
3
1
1
1
2
2
1
3
2
1
3
0
1
2
3
1
1
243 DISC
158
S. Colombini et al.
Figure 1. Recurrent indolent lip ulcer on the left upper lip of a cat with ea allergy dermatitis. Notice the biopsy scar on the right upper lip
from a previous indolent lip ulcer.
243 DISC
Feline ea allergy and lip ulcers
appeared to be protective against the development of
FAD in cats. This discrepancy may reect the limited
number of cats in the current study.
There was no association between clinical signs of
FAD and positive results on diagnostic testing.
Response to strict ea control based on clinical
suspicion of FAD remains the optimal diagnostic
test. Both whole ea antigen (Greer Laboratories)
and ea salivary antigen (Heska Corp.) were utilized
in the IDST. Due to the increased specicity of the
ea salivary antigen, as compared with the crude
whole ea antigen, it was expected that this would be
a better indicator of clinical disease. No association
could be found, however, between the development
of clinical signs and positive results on IDST to either
antigen. Likewise, there was no association between
clinical signs and positive in vitro results. The fact
that two of the cats in this study, from a SPF (eanaive) breeding colony, had positive in vitro titres at
the start of the study raises concerns as to the
reliability of the test. Because the in vitro test
specically measures IgE reactive with ea salivary
antigens, these ea-naive cats should not have had
positive titres. Reasons for the discrepancy between
clinical signs and results of diagnostic testing
may include the limited number of cats in this
study or it may reect inherent aws in the diagnostic
tests themselves.
A greater number of cats had positive IDST and in
vitro results at 240 days, vs. 120 days. However, only
half of the cats received ea exposure during the
initial 120 days of the study. It is possible that a
longer duration of ea exposure is required to obtain
positive conversion. The endpoint of 120 days was
chosen based on previous clinical observations by
CSF that most cats become ea allergic between 100
and 120 days. Repetitive IDST may also eventually
result in positive conversion, which is why IDST was
kept to a minimum in the current study.
Half of the cats in this study developed indolent lip
ulcers, a much higher incidence than is suspected to
occur in the natural population. The high incidence
of lip ulcers in these related cats supports a genetic
inuence, suggested by previous reports.8 The ulcers
spontaneously regressed in all ve cats even with
continued ea exposure, but recurred in four cats.
The recurrent lip ulcers did not subsequently regress
in two of the cats, however, until ea exposure was
discontinued. None of the cats in the current study
had any history of lip ulcers until they were exposed
to eas and all of the cats had other clinical signs of
ea allergy dermatitis, suggesting a combined genetic
and allergic etiopathogenesis. It should be noted that
the cats in this study were between 6 and 8 months of
age at the start of the study. This would be young for
the typical onset of lip ulcers. However, three of the
four cats that developed recurrent lip ulcers during
the study were kept for 7 months after the study
ended and ea exposure had been discontinued. None
of the three cats developed further lip ulcers during
159
243 DISC
160
S. Colombini et al.
ACKNOWLEDGEMENTS
The authors would like to thank the American College
of Veterinary Dermatology and Louisiana State
University Department of Veterinary Clinical
Sciences, whose grants supported this study and Heska
Corp. for their skin test antigens and in vitro testing.
The authors would also like to acknowledge Ms. Gaye
Gomila for her invaluable technical assistance.
REFERENCES
1. Halliwell, R.E.W. Flea allergy pathogenesis,
diagnosis and therapy. The North American
Veterinary Conference Proceedings. pp. 1201, 1993.
2. Scott, D.W., Miller, W.H., Grin, C.E. Immunologic
skin diseases. In: Scott, D.W., Miller, W.H., Grin,
C.E., eds. Small Animal Dermatology, 5th edn.
Philadelphia: W.B. Saunders, 1995: 484626.
3. Moriello, K.A., McMurdy, M.A. The prevalence of
positive intradermal skin test reactions to ea extract in
clinically normal cats. Companion Animal Practice
1989; 19: 2830.
4. Foster, A.P., O'Dair, H. Allergy testing for skin disease
in the cat In vivo vs In vitro tests. Veterinary
Dermatology 1993; 4: 1115.
5. Slacek, B., Opdebeeck, J.P. Reactivity of dogs and cats
to feeding eas and to ea antigens injected
intradermally. Australian Veterinary Journal 1993; 70:
3134.
6. Plant, J.D. Recognizing the manifestations of ea
allergy in cats. Veterinary Medicine 1991; 86: 4826.
7. McCall, C.A., Stedman, K.E., Bevier, D.E., Kunkle,
G.A., Foil, C.S., Foil, L.D. Correlation of feline IgE,
determined by FceR1a-based ELISA technology, and
IDST to Ctenocephalides felis salivary antigens in a feline
model of ea bite allergic dermatitis. Clinical Advances:
Supplement to Compendium on Continuing Education for
the Practicing Veterinarian 1997; 19: 2932.
8. Power, H.T., Ihrke, P.J. Selected feline eosinophilic
skin diseases. Veterinary Clinics of North America:
Small Animal Practice 1995; 25: 83350.
Resume Les buts de cette etude etaient multiples: caracteriser le role d'une exposition intermittente ou
chronique a des puces sur le developpement d'une dermatite par allergie aux piqures de puces (DAPP) chez le
chat, evaluer la valeur des tests cutanes intradermiques (IDST) et des tests in vitro, et etudier l'incidence et les
caracteristiques histopathologiques des ulceres labiaux atones. Dix chats non exposes anterieurement aux
puces ont ete divises en deux groupes. Un groupe a ete expose a des puces de facon intermittente pendant 120
jours. Puis les deux groupes ont ete exposes a des puces de facon permanente pendant 120 jours
supplementaires. Des tests serologiques in vitro et des IDST (corps totaux de puces et antigenes salivaires) ont
ete realises. Huit chats sur 10 ont developpe des symptomes typiques de DAPP apres 3 mois, et 5 de ces 8 chats
ont presente un ulcere atone, caracterise a l'examen histopathologique par une ulceration avec un inltrat
inammatoire de polynucleaires neutrophiles et des images de colonisation bacterienne de surface. Aucune
association n'a ete observee entre les signes cliniques et les resultats des IDST ou des tests in vitro. Aucune
dierence clinique n'a ete observee entre les deux groupes de chats. [Colombini, S., Clay Hodgin, E., Foil, C.
S., Hosgood, G., Foil, L. D. Induction of feline ea allergy dermatitis and the incidence and histopathological
characteristics of concurrent indolent lip ulcers. (Incidence et aspects histopathologiques des ulceres labiaux
atones chez la chat apres induction d'une dermatite par allergie aux piqures de puces.) Veterinary Dermatology
12: 155161.]
Resumen Los objetivos de este estudio fueron caracterizar el papel de la exposicion continua contra la
exposicion intermitente a pulgas en el desarrollo de la dermatitis alergica a pulgas (DAP) en gatos, valorar la
precision del test cutaneo intradermico (TCID) y las pruebas in vitro, y documentar la incidencia y las
# 2001 Blackwell Science Ltd, Veterinary Dermatology, 12, 155161
243 DISC
Feline ea allergy and lip ulcers
161
caracter sticas histopatologicas de las ulceras labiales indolentes. Se separaron diez gatos nunca antes
expuestos a pulgas en dos grupos. Un grupo recibio una exposicion intermitente a pulgas durante 120 d as.
Despues, ambos grupos recibieron una exposicion continua a pulgas durante 120 d as. Se realizaron pruebas
in vitro para anticuerpos salivares y TCID utilizando tanto antigeno completo de pulga como antigeno salivar
de pulga. Ocho de 10 gatos desarrollaron s ntomas cl nicos de DAP dentro de los primeros 3 meses y cinco de
estos ocho gatos desarrollaron ulceras labiales que se caracterizaban histopatologicamente por ulceracion con
inamacion predominantemente neutrof lica y colonizacion bacteriana supercial. No exist a relacion entre la
presencia o ausencia de s ntomas cl nicos y los resultados positivos del IDST o de las pruebas in vitro, y no se
observo diferencia en el desarrollo de s ntomas cl nicos entre los dos grupos de gatos. [Colombini, S., Clay
Hodgin, E., Foil, C. S., Hosgood, G., Foil, L. D. Induction of feline ea allergy dermatitis and the incidence and
histopathological characteristics of concurrent indolent lip ulcers. (Induccion de la dermatitis alergica a pulgas y
la incidencia y caracter sticas histopatologicas de las ulceras indolentes labiales concurrentes.) Veterinary
Dermatology 12: 155161.]
Zusammenfassung Die Ziele dieser Studie waren die Charakterisierung der Rolle von periodischer im
Gegensatz zu lang andauernder Flohexponierung in der Entwicklung der Flohbissallergie (FBA) der Katze,
die Prufung der Genauigkeit von Intrakutantests (IKT) und Serumtests, und die Dokumentation der
Haugkeit und histopathologischen Eigenschaften des eosinophilen Geschwurs. Zehn oh-naive Katzen
wurden in zwei Gruppen aufgeteilt. Eine Gruppe wurde fur 120 Tage periodisch Flohbissen ausgesetzt.
Danach wurden beide Gruppen ununterbrochen fur 120 Tage Flohbissen ausgesetzt. In vitro-Tests auf
Speichel-Antigene des Flohs und IKT mit Flohantigen und Speichel-Antigen des Flohs wurden durchgefuhrt.
Acht von 10 Katzen zeigten klinische Symptome von FBA innerhalb von 3 Monaten, funf dieser acht Katzen
bekamen Lippengeschwure, die histopathologisch durch Geschwurbildung mit uberwiegend neutrophiler
Entzundung und bakterieller Oberachenbesiedlung gekennzeichnet waren. Es gab keine Korrelation
zwischen dem Vorhandensein oder dem Fehlen klinischer Symptome und positivem IKT oder den
Ergebnissen der Serumtests, und keinen Unterschied hinsichtlich der klinischen Symptome zwischen den
zwei Gruppen. [Colombini, S., Clay Hodgin, E., Foil, C. S., Hosgood, G., Foil, L. D. Induction of feline ea
allergy dermatitis and the incidence and histopathological characteristics of concurrent indolent lip ulcers. (Die
Induktion von Flohbissallergie bei der Katze und die Haugkeit und histopathologischen Eigenschaften von
gleichzeitigen eosinophilen Geschwuren.) Veterinary Dermatology 12: 155161.]