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Abstract Ten Chesapeake Bay retriever (CBRS) dogs with hair loss were recruited in collaboration with the
American Chesapeake Club. All dogs had nonpruritic, noninflammatory, regionalized hair loss affecting the same
areas of the body in male and female dogs. Hormonal investigations showed increased adrenal and sex steroid
concentration in seven cases. Histopathology revealed follicular hyperkeratosis and plugging, follicular atrophy,
and occasional melanin clumping with malformed hair shafts. This study suggests that hair loss in CBRS is a
breed syndrome in which young adult dogs have hair loss characterized by unusual histological features and
abnormal steroid production. A familial predisposition seems likely and selective breeding might reduce the
occurrence of this condition.
IN TRO D U CT I ON
Adult-onset, nonpruritic, symmetrical or generalized
hair loss in dogs is commonly caused by endocrine disorders such as hyperadrenocorticism, hypothyroidism,
and hyperestrogenism due to testicular Sertoli cell
tumour. In some breeds such as Nordic breeds, miniature poodle and water spaniel dogs, there is an adultonset form of hair loss in which the pathogenesis is still
not completely clear.13 Both male and female dogs,
neutered or intact, are affected. Symmetrical hair loss
develops around the neck, and over the trunk, flanks,
caudal thighs and/or perineum. Apart from the coat
changes, the dogs seem to be healthy and the results of
routine adrenocortical and thyroid function tests have
been reported to be normal.
In the last few years, CBR breeders have started to
recognize coat disorders characterized by areas of hair
loss affecting the axillae, latero-ventral thorax, flanks,
ventrum, dorsum, rump and/or the caudal part of the
thighs in both male and female dogs.
The purpose of this study was to describe in detail
the clinical aspects of hair loss in CBRS, to evaluate
their hormonal status, and to review the histopathology of the skin from affected and unaffected areas from
dogs. The dogs were those recruited for the study and
those available from the archives of the Dermato-
M AT E R IA L S A N D M E T H O D S
Epidemiological survey
In September 2002, the American Chesapeake Club
(ACC) was contacted regarding the occurrence of hair
loss in this breed. Owners and breeders of CBRS with
nonpruritic, regionalized hair loss were solicited by a
letter published in the ACC Newsletter and also sent by
the ACC List Server. The respondents reporting dogs
with this pattern of hair loss were invited to participate
in a clinical study by either coming to the MJ Ryan
Veterinary Hospital of the University of Pennsylvania
(MJR-VHUP) or going to their local veterinarian. In
each case, the veterinarian and owner received a copy
of the protocol of the tests to be carried out, and the
veterinarian was mailed a package including 1 dose of
adrenocorticotrophic hormone (ACTH) and tubes for
storing the blood and skin specimens. They were asked
to send back the samples with ice packs and to send the
parcel containing the samples by courier.
Clinical study
This study was presented as a free communication at the Fifth World
Congress of Veterinary Dermatology Vienna, Austria, August 25
28, 2004.
Correspondence: R. Cerundolo, Department of Clinical Studies,
School of Veterinary Medicine, University of Pennsylvania, 3900
Delancey Street, Philadelphia PA 19104, USA. E-mail:
cerundol@vet.upenn.edu
2005 European Society of Veterinary Dermatology
40
R Cerundolo et al.
Blood investigations
Blood was collected by jugular venipuncture for
routine haematological and biochemical investigations.
Two aliquots of the serum were stored at 20 C for
hormonal assay. One was sent to Michigan State University for a thyroid panel to measure: total thyroxine
(T4), total triiodothyronine (T3), free T4 by equilibrium dialysis (fT4 ED), free T3 (fT3), T4 and T3
autoantibody (T4AA, T3AA), thyroid stimulating hormone (TSH), and thyroglobulin autoantibody (TgAA);
insulin-like growth factor 1 (IGF1) was also measured.
The second half of the serum was sent to the University
of Tennessee for a sex-hormone panel to measure the
hormone basal concentration. A second blood sample
was collected 1 hour after intravenous administration
of 0.25 mg dog1 of tetracosactrin acetate (Synacthen;
Alliance Pharmaceuticals Ltd., Chippenham, Wilts, UK).
The hormones measured in both samples included cortisol, 17-hydroxyprogesterone (17-OHP), androstenedione, estradiol, progesterone and testosterone.
The source of reagents, as well as assay procedures
and suitability for use in canine serum, has previously
been reported for all thyroid-related tests, with the
exception of fT3. Validation data for T4 and TSH,4
T3,5 fT4 ED,6 T4AA and T3AA,7 and TgAA8 have
been described. Free T3 was measured using a directserum analogue-based radioimmunoassay kit (Clinical
Assays Gammacoat Free T3 125I RIA Kit, DiaSorin
Inc., Stillwater, MN, USA). The manufacturers protocol for the assay was followed with the exception that
the incubation of antibody-coated tubes containing
radioligand and sample was extended to 3 h in a 37 Cwater bath. The manufacturer of the kit described
antibody specificity of 100% cross-reactivity with triiodothyronine and less than 0.02% cross-reactivity with
all other iodothyronines evaluated. The analytic sensitivity of the assay, defined as the concentration of fT3
at 90% specific binding, was 1.1 pmol L1 (10 assays).
In direct-serum analogue-based assays of free thyroid
hormones, there are equilibrium reactions between the
hormone measured, endogenous binding proteins, and
the assay antibody. As a result, assessment of recovery
and dilutional parallelism is not applicable as in a
standard radioimmunoassay. For canine serum pools
of fT3 concentrations of 2.5 and 13.8 pmol L1, respective intra-assay coefficients of variation (CV) were 0.064
and 0.059 and respective interassay CV were 0.138 and
0.051 (n = 10 replicates).
Insulin-like growth factor 1 (IGF1) was measured in
canine serum samples with a commercially available
radioimmunoassay kit (IGF-1 Insulin-like growth
factor by extraction, Nichols Institute Diagnostics,
San Clemente, CA, USA). An acid-ethanol solution
consisting of 12.5% 2 N HCl/87.5% absolute ethanol
(% by volume) was prepared following the manufacturers instructions. Extraction of sera and radio-
Urine investigations
Owners were also asked to collect morning urine
samples on 10 consecutive days. For this purpose, the
owners were provided with 10 polypropylene tubes in a
package with ice packs, to be sent back to MJR-VHUP
by courier. In each sample, the corticoid/creatinine
ratio (UCCR) was determined according to a procedure described,11 and the average of the 10 ratios was
subsequently calculated for each dog.
Histopathology
Three or four 6-mm punch biopsy specimens of skin
were collected under local anaesthesia using 2%
lidocaine from eight CBRs. Specimens were obtained
from one or more areas with hair loss on the flanks,
rump and thigh. One specimen, to serve as a control,
was collected in each case from a clinically normal
area, which was most often the dorsal thorax. Specimens were fixed in 10% neutral buffered formalin and
transferred to the DS-UPENN for processing and
examination. These were bisected vertically, along the
line of the hair where possible, and paraffin sections
that had been stained with haematoxylin and eosin
were prepared from one half of each sample using
standard histological methods. All sections were
41
Table 1. Clinical sites of hair loss in affected dogs included in this study
Cases
Age (years)
Sex
Ventrolateral thorax
Axillae
Flanks
Abdomen
Thighs
Rump
1
2
3
4
5
6
7
8
9
10
2
6
2
2
4
3
3
3
2
1 1 /2
F
NM
NM
F
NM
F
NF
NF
F
F
v
x
v
x
v
x
v
v
v
x
v
x
v
v
v
x
v
x
x
x
x
v
v
v
v
v
v
v
v
v
v
x
x
v
v
x
v
x
x
x
v
v
v
v
v
x
v
v
x
x
x
x
x
x
x
x
x
v
v
x
Figure 1. Extensive hair loss affecting the lateral side of the body (a), the rump (b) and the thighs (c).
initially examined blind (i.e. without prior knowledge of the condition or site of the skin sampled).
Results were subsequently reviewed in relation to the
clinical findings. Three of the dogs had already been
biopsied by board-certified dermatologists. Skin sections from 11 additional cases were identified from
the archives of the DS-UPENN (six cases) and the
DSS-UTVMC (five cases). These cases were selected
through a computer search using keywords Chesapeake Bay retriever and noninflammatory alopecia
in conjunction with compatible historical and clinical
findings.
Pedigree analysis
Four-generation pedigrees of six dogs were available.
RESU LTS
Responses from the ACC members were high and 24
owners of affected dogs agreed to collaborate. Due to
funding restraints, only the first 10 people who replied
were contacted and their dogs recruited. Four were
examined at MJR-VHUP, while six dogs were seen and
sampled by the local veterinarians. There were seven
female dogs (two of which had been spayed) and three
neutered male dogs. Nine of the dogs were between 1.5
and 4 years of age (median 2.5 years); only dog 2 was
6 years old but hair loss had started 2 years previously.
Laboratory investigations
Routine haematological and biochemical investigations gave values that were within normal limits in all
cases (data not shown).
Hormonal assays showed normal thyroid hormone
concentrations in all dogs except for dog 4 which had
42
R Cerundolo et al.
Table 2. Clinical details, cortisol/creatinine ratio and thyroid panel results of the affected dogs included in this study
Cases
Age
(years)
Sex
NM
NM
NM
7
8
3
3
NF
NF
10
1.5
Reference range
Urine
C/C ratio
mean
710
7.8
69
7.3
612
8.8
810
8.6
1013
11.2
69
7.8
ND
68
6.57
612
9.6
56
5.7
824
TSH
mU I1
TgAA
T4
nmol L1
T3
nmol L1
FT4 ED
pmol L1
FT3
pmol L1
T4AA
T3AA
IGF 1
nmol L1
13
93
93
0.5*
4.3*
13
29.5
28
105
34
1.2
14
3.5*
13
11.8
13
89
35
1.5
15
8.2
38.3
38
270
26
0.2*
15
5.3
45
30
20
71
55
0.2*
12
6.7
33
17
75
34
1.0
18
5.5
41.3
ND
59
ND
1.8
ND
22
ND
6.5
ND
5
ND
1
ND
53.1
ND
11
ND
76
16
53
55
1.0
28
8.3
ND
13
32
33
1.1
19
10.8
ND
1567
1.02.5
037
< 200%
642
4.512
< 20%
< 10%
5 45
*Values are below the reference range. Values above the reference range are in bold; M, intact male dog; NM, neutered male dog; F, intact female
dog; NF, neutered female dog.
Histopathological findings
A total of 53 skin biopsy specimens from 14 CBRs submitted at the DS-UPENN and from five CBRs submitted at the DSS-UTVMC were examined. Eight 6-mm
biopsies from clinically normal sites were received from
eight CBRs in the clinical study. Two biopsy specimens
from two dogs were unavailable for review. These cases
had been interpreted by a board-certified veterinary
pathologist with expertise in dermatopathology, and
had similar histological findings as in our cases. These
cases were selected by the description of the pattern of
hair loss mentioned in the history submitted with the
skin samples, and were suggestive of this condition. Of
Follow-up
The owners of two dogs (1 and 4) had their bitches
spayed after the first examination. In both dogs no hair
re-growth was evident 5 and 6 months, respectively,
after spaying.
Pedigree analysis
Analysis of six pedigrees of affected dogs revealed
common ancestors in both the sire and the dam line of
all dogs except dog 9.
D ISC U S S IO N
This study is the first to describe the clinical findings,
hormonal status and histopathology of a noninflammatory
0.46 22.1
0.02 0.42
0.03 0.1
0.02 0.45
43
*Values are below the reference range. Values above the reference range are in bold; M, intact male dog; NM, neutered male dog; F, intact female dog; NF, neutered female dog.
0.1926.3
0.01 0.24
0.01 0.1
0.01 0.32
0.55 1.70
0.221.45
0.33 4.33
0.101.50
0.02 0.4
0.01 0.17
0.03 2.16
0.01 0.49
30.0 65.6
23.3 69.4
31.8 63.1
27.9 69.2
6.8 79.2
2.4 29.0
3.8 42.1
2.739.7
2.1 42.6
0.13.6
1.9 11.9
0.15.7
Reference range
M
NM
F
NF
2.5 56.7
2.0 56.5
4.0 59.9
2.158.8
70.8 108.5
70.6 151.2
66.7174.8
65.0 174.6
0.06 0.84
0.01 0.22
0.05 0.69
0.01 0.07
0.372.87
0.25 2.63
0.68 4.44
0.40 1.62
30.5 66.6
23.1 65.1
31.5 65.4
30.8 69.9
Post
Pre
0.03
0.03
0.02
0.03
0.04
0.03
0.03
0.03
0.01
0.03
Post
4.1
1.96
1.11
3.29
1.03
2.23
1.75
0.96
1.50
5.71
Pre
2.7
0.37
0.23
0.27
0.53
0.08
0.05
0.01
0.08
3.36
77.4
56.6
73.9
40.2
47
60.4
26.1*
56.9
61.2
57.7
77.2
54.6
72.2
41.4
47.4
61.8
22*
57.1
56.1
60.2
43.0
66.2
15.5
27.5
12.7
35.6
20.7
17
13.4
18.7
14.9
12.4
5.4
4.4
12.8
4.3
2.7
0.6
2.3
8.8
4.75
2.12
0.78
11.5
2.23
3.04
1.98
0.83
1.46
3.81
Post
Pre
Post
Pre
Post
1.04
0.41
0.20
0.76
0.81
0.14
0.08
0.06
0.12
1.15
Pre
Post
124.5
157.5
133
103.4
105.1
109.9
95
72.5
113.8
64.3
47.8
68.8
37.9
15.4
68.0
8.8
11.4
7.4
14.5
66.9
Pre
2
6
2
2
4
3
3
3
2
1.5
1
2
3
4
5
6
7
8
9
10
Sex
Age
(years)
Cases
F
NM
NM
F
NM
F
NF
NF
F
F
Testosterone
ng mL1
Progesterone
ng mL1
Estradiol
pg mL1
Androstenedione
ng mL1
17-OHP
ng mL1
Cortisol
ng mL1
Table 3. Clinical details, adrenal and sex steroid results of the affected dogs included in this study
0.03
0.03
0.02
0.04
0.04
0.05
0.03
0.03
0.02*
0.04
44
R Cerundolo et al.
6.
7.
8.
9.
10.
ACKN OWLEDGE ME NT S
The authors are grateful to the veterinarians Drs D.
Gram, M. Guise, R. Mowday, M. Stankovics, E. Robinson, E. Rothstein, T. Tapp and N. Schoulberg for
their help in sampling most of the affected dogs. We are
also grateful to Dr Kelly Credille for providing copies
of the skin sections from the archive of the Dermatopathology Specialty Service of the University of Texas
Veterinary Medical Center (DSS-UTVMC). We would
like to thank the owners of affected dogs and the members of the American Chesapeake Club for their collaboration, and in particular Ms Baldwin for helping to
gather information on the CBR history. This study was
sponsored by the University of Pennsylvania, Departmental Research Grant.
11.
12.
13.
14.
15.
REFEREN CE S
16.
1. Cerundolo R, Lloyd DH, McNeil PE et al. An analysis
of factors underlying hypotrichosis and/or alopecia in
Irish water spaniels in the United Kingdom. Veterinary
Dermatology 2000; 11: 10722.
2. Cerundolo R, Lloyd DH, Mol JA et al. Alopecia X in
Pomeranians and miniature poodles is associated with
abnormal pituitary-adrenal function. Journal of Veterinary Internal Medicine in press.
3. Schmeitzel LP. Alopecia X of Nordic breeds. In: Proceedings 15th Annual Members Meeting AAVD and
ACVD. Maui, Hawaii, 1999: 1317.
4. Paradis M, Sauve F, Charest J et al. Effects of moderate
to severe osteoarthritis on canine thyroid function.
Canadian Veterinary Journal 2003; 44: 40712.
5. Panciera DL, MacEwen EG, Atkins CE et al. Thyroid
function tests in euthyroid dogs treated with 1-thyroxine.
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19.
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21.
45
Rsum Dix Chesapeake Bay retriever (CBR) prsentant une chute de poils ont t slectionns en collaboration avec le American Chesapeake Club. Tous les chiens prsentaient une perte de poils non prurigineuse, non
inflammatoire, localise, touchant les mmes zones chez les mles et chez les femelles. Les tudes hormonales ont
montr une augmentation des concentrations des hormones sexuelles surrnaliennes dans sept cas. Lexamen
2005 European Society of Veterinary Dermatology, Veterinary Dermatology, 16, 3946
46
R Cerundolo et al.
histopathologique a montr une hyperkratose folliculaire et une atrophie associe des bouchons de kratine,
parfois associs des aggrgats de mlanine dans des poils malforms. Cette tude suggre que la chute de poils
dans la CBR est un syndrome dans lequel une anomalie de la production de stroides est prsente. Une prdisposition familiale semble probable et une reproduction slective pourrait diminuer lincidence de cette maladie.
Resumen Se seleccionaron diez perros Retriever de Chesapeake Bay (CBR) con prdida de pelo, en colaboracin con el Club Americano del Chesapeake. Todos los perros mostraban una prdida de pelo no-prurtica,
no-inflamatoria, regionalizada, afectando las mismas zonas corporales en machos y hembras. Las investigaciones
hormonales mostraron concentraciones elevadas de esteroides adrenales y gonadales en siete casos. La histopatologa revel una hiperqueratosis y obturacin folicular, atrofia folicular, y agregados ocasionales de melanina
con pelos malformados. Este estudio sugiere que la prdida de pelo en el CBR es un sndrome de la raza en el
que los perros adultos jvenes padecen una prdida de pelo caracterizada por caractersticas histolgicas inusuales y produccin anormal de esteroides. Parece probable una predisposicin familiar y la cra seleccionada
podra reducir la incidencia de esta enfermedad.
Zusammenfassung 10 Chesapeake Bay Retriever (CBR) mit Haarverlust wurden in Zusammenarbeit mit
dem American Chesapeake Club rekrutiert. Alle Hunde hatten nicht juckenden, nicht entzndlichen, regionalen
Haarausfall, der sich bei mnnlichen und weiblichen Tieren auf die gleichen Krperregionen erstreckte. Hormonuntersuchungen zeigten bei sieben Fllen erhhte adrenale und Geschlechts-Hormonkonzentrationen. Die
Histopathologie zeigte follikulre Hyperkeratose und Anschoppung, follikulre Atrophie und gelegentliche Melaninverklumpung in malformierten Haarschften. Diese Studie lt vermuten, dass Haarausfall in CBR eine
Rasseerkrankung ist, bei denen junge erwachsene Hunde Haarausfall haben, der durch unbliche histologische
Eigenschaften und anormale Steroidproduktion charakterisiert ist. Eine familire Prdisposition erscheint wahrscheinlich und selektives Zchten mag das Auftreten dieser Erkrankung reduzieren.