Adult-onset Hair Loss In Chesapeake Bay Retrievers- A Clinical And Histological Study (pages 39–46) 14401c

Veterinary Dermatology 2005, 16, 39– 46

Adult-onset hair loss in Chesapeake Bay retrievers: a clinical and histological study

Blackwell Publishing, Ltd.

R. CERUNDOLO*, E. A. MAULDIN†, M. H. GOLDSCHMIDT†, S. L. BEYERLEIN‡, K. R. REFSAL‡ and J. W. OLIVER§ *Department of Clinical Studies and †Department of Pathobiology, University of Pennsylvania, Philadelphia, USA ‡Endocrine Section, Diagnostic Center for Population and Animal Health, Michigan State University, Lansing, USA §Clinical Endocrinology Service, University of Tennessee, Knoxville, USA (Received 20 July 2004; accepted 21 September 2004)

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.1–3 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-

pathology Service of the University of Pennsylvania (DS-UPENN) and the Dermatopathology Specialty Service of the University of Texas Veterinary Medical Center (DSS-UTVMC). Pedigree data relating to affected dogs were also collected and analysed.

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 ed 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: [email protected] © 2005 European Society of Veterinary Dermatology

Four of the 10 cases were examined at MJR-VHUP and a general and dermatological examination was performed. Routine dermatological investigations (skin scrapings, coat brushings for fleas and trichogram) and fungal culture were undertaken in these cases. Six of the 10 cases were examined by the referring veterinarians 39

40

R Cerundolo et al.

(three of these dogs were seen by three Board-certified dermatologists). Intact bitches were examined during diestrus, roughly 2 months after their oestrus cycle.

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 ’ 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 ’ to measure the hormone basal concentration. A second blood sample was collected 1 hour after intravenous istration of 0.25 mg dog−1 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 manufacturer’s 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 L−1 (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 L−1, 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 manufacturer’s instructions. Extraction of sera and radio-

immunoassays were performed with reagent volumes and incubation times specified in the manufacturer’s protocol. The manufacturer of the kit described essentially no antibody cross-reactivity with other peptide hormones including growth hormone, thyrotropin, luteinizing hormone, prolactin, porcine insulin and proinsulin, or insulin-like growth factor II. The sensitivity of the assay, defined as the concentration of IGF1 at 90% specific binding, was 2.1 nmol L−1 (mean of 10 assays). When IGF1 was added to each of two extracted samples at amounts of 19, 36 and 75 nmol L−1, the average rates of recovery in the assay were 77%, 80% and 85%, respectively. A canine serum sample with measured concentration of 118 nmol L−1 was diluted at rates of 50%, 25% and 12.5% with reagent phosphate buffer prior to extraction. When the results were corrected for dilution, 105%, 130% and 100% recovery of the expected value was obtained for the respective dilutions. Intra-assay repeatability was assessed with three pools of canine sera assembled to have ‘lower’ (17 nmol L−1), ‘mid-range’ (51 nmol L−1), and ‘high’ (118 nmol L−1) concentrations. The respective intra-assay coefficients of variation for 10 extracted samples of each pool were 0.118, 0.053, and 0.068. In 10 assay runs, the interassay CV of the same serum pools were 0.254, 0.131 and 0.160, respectively. The ‘sex-hormone ’ hormones were measured using human kits that have been previously validated for the dog.9,10 The sensitivity of the hormone assay is: testosterone (0.04 ng mL−1); androstenedione (0.05 ng mL−1); 17-OHP (0.08 ng mL−1); progesterone (0.03 ng mL−1); estradiol (7.2 pg mL−1); cortisol (0.2 µg/dL). Normal reference range for the two laboratories is given in Table 1.

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

© 2005 European Society of Veterinary Dermatology, Veterinary Dermatology, 16, 39– 46

Hair loss in Chesapeake Bay retrievers

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

v, affected area; x, nonaffected area.

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 were high and 24 owners of affected dogs agreed to collaborate. Due to funding restraints, only the first 10 people who replied were ed 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.

In dog 4 hair loss had started at 5 months of age, and in dog 5 hair loss had started at 2 years of age soon after castration. Dog 5 had previously been treated for 2 years with melatonin without showing hair re-growth. Dogs 3 and 8 had had several episodes of superficial pyoderma, which had resolved with antibiotic therapy but no hair re-growth had occurred following the resolution of the pyoderma.

Clinical findings in dogs with coat disorders General physical examination revealed no significant findings. Dermatological examination revealed various patterns of hair loss ranging from sparse hair to complete baldness in various sites such as the axillae (dogs 1, 3–6, 7), ventrum (1, 4, 5, 7), flanks (2–10), rump (8, 9), latero-ventral thorax (1, 3, 5, 7–9), or the thighs (1– 5, 7, 8) (Fig. 1a,b,c; Table 1). No differences in the location of hair loss were seen in this group of dogs between sexes. The owner of dog 10 felt that hair loss was more prominent during the oestrus cycle, with subsequent poor hair re-growth.

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

© 2005 European Society of Veterinary Dermatology, Veterinary Dermatology, 16, 39–46

42

R Cerundolo et al.

Table 2. Clinical details, cortisol/creatinine ratio and thyroid results of the affected dogs included in this study

Cases

Age (years)

Sex

1

2

F

2

6

NM

3

2

NM

4

2

F

5

4

NM

6

3

F

7 8

3 3

NF NF

9

2

F

10

1.5

F

Reference range

Urine C/C ratio mean 7–10 7.8 6–9 7.3 6–12 8.8 8–10 8.6 10–13 11.2 6–9 7.8 ND 6–8 6.57 6–12 9.6 5–6 5.7 8–24

TSH mU I−1

TgAA

T4 nmol L−1

T3 nmol L−1

FT4 ED pmol L−1

FT3 pmol L−1

T4AA

T3AA

IGF 1 nmol L−1

13

93

93

0.5*

8

4.3*

13

5

29.5

28

105

34

1.2

14

3.5*

13

3

11.8

13

89

35

1.5

15

8.2

9

3

38.3

38

270

26

0.2*

15

5.3

0

45

30

20

71

55

0.2*

12

6.7

4

0

33

17

75

34

1.0

18

5.5

8

1

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

3

3

ND

13

32

33

1.1

19

10.8

9

6

ND

15–67

1.0–2.5

0–37

< 200%

6–42

4.5–12

< 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.

slightly increased concentrations of T3AA, TSH and TgAA. Normal IGF1 concentrations were seen in all cases except for dog 8 (Table 2). The ‘sex-hormone ’ found slightly increased cortisol concentration pre-ACTH in dogs 2, 5 and 10 and post-ACTH in dog 2; increased 17-OHP concentrations pre-ACTH in dogs 1, 2, 4 and 10, and post-ACTH in dogs 1, 4 and 7; increased androstenedione concentration pre-ACTH in two neutered male dogs (nos. 2, 3) and one female dog (no. 1) and post-ACTH in one female dog (no. 1) and one neutered male (dog 2); slightly increased oestrogen concentration pre- and post-ACTH in one female dog (no. 1) and one neutered male dog (no. 3); increased progesterone concentration pre-ACTH in three neutered male dogs (nos. 2, 3, 5) and two female dogs (nos. 1, 10), and post-ACTH in one neutered male dog (no. 2), one neutered female dog (no. 7) and one female dog (no. 10) (Table 3). The testosterone concentrations were within the reference range although most results for this hormone were below assay sensitivity. The UCCRs were within the normal range in all dogs.

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

the 14 dogs, 13 had mild to moderate nonscarring alopecia in affected sites. Follicular infundibula were dilated and distended with keratin. The hyperkeratosis extended into secondary follicles and sebaceous glands ducts, producing an abnormally globose shape to the infundibular region (Fig. 2a). Atrophy of primary and secondary follicles was evident, but secondary follicles were more severely affected. Some follicles were miniaturized. Distended infundibula contained small, contorted hair shafts with irregular melanin clumping and loss of corticomedullary distinction (eight dogs) (Fig. 2a,b). Changes were the same in all sites (except normal skin). Flame follicles were seen in dog 8 only. Sebaceous glands were consistently normal to hyperplastic in relation to the body site sampled. Dog 2 had multifocal folliculitis in one of the initial biopsies. A repeat biopsy from a noninflammed alopecic area revealed pronounced infundibular hyperkeratosis, similar but less severe than the remaining cases.

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

© 2005 European Society of Veterinary Dermatology, Veterinary Dermatology, 16, 39– 46

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.

0.19–26.3 0.01– 0.24 0.01– 0.1 0.01– 0.32 0.55 –1.70 0.22–1.45 0.33 – 4.33 0.10–1.50 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 2.7–39.7 2.1– 42.6 0.1–3.6 1.9 –11.9 0.1–5.7 Reference range

M NM F NF

2.5 –56.7 2.0 –56.5 4.0 –59.9 2.1–58.8

70.8 –108.5 70.6 –151.2 66.7–174.8 65.0 –174.6

0.06 – 0.84 0.01– 0.22 0.05– 0.69 0.01– 0.07

0.37–2.87 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 mL−1 Progesterone ng mL−1 Estradiol pg mL−1 Androstenedione ng mL−1 17-OHP ng mL−1 Cortisol ng mL−1

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

Hair loss in Chesapeake Bay retrievers

Figure 2. (a) Note the pronounced distension of follicular infundibula by marked orthokeratotic hyperkeratosis. Bar = 400 µm. (b) Higher magnification of (a). Dystrophic hair shafts with abnormal melanin clumping. Bar = 200 µm.

alopecic disorder unique to Chesapeake Bay retrievers. This disorder has generated a great deal of confusion among breeders and veterinary practitioners for many years. Many cases were misdiagnosed as hypothyroidism and failed to respond to hormonal replacement therapy. The most common presentation in our dogs was thinning to complete hair loss on the axillae, flanks, abdomen and caudal thighs. Most cases had no accompanying inflammation. This pattern of hair loss is similar to that seen in cyclic flank alopecia, canine pattern baldness and greyhound bald thigh syndrome.12,13 The dogs were otherwise healthy and the hair loss did not respond to hair growth stimulants (thyroxine, melatonin). Furthermore, the hair growth and loss did not appear to cycle. The term follicular dysplasia has been reported in many breeds but the term is loosely applied to both disorders of hair cycling (e.g. canine recurrent flank alopecia),14,15 as well as true anagen-based structural defects in hair shaft production (e.g. colour dilution alopecia, black hair follicular dysplasia).16,17 The Chesapeake Bay retriever has previously been cited as

© 2005 European Society of Veterinary Dermatology, Veterinary Dermatology, 16, 39–46

44

R Cerundolo et al.

a breed predisposed to ‘follicular dysplasia’ but not further defined.12 Clinically, our cases differ from canine recurrent alopecia in that (1) the alopecia is always multifocal (not confined to the flank area) with a unique distribution and (2) the hair growth does not cycle with the seasons of the year. Histologically, our cases had a spectrum of changes and some were very similar, if not identical, to recurrent flank alopecia. Common changes were pronounced infundibular hyperkeratosis with misshapen telogen follicles. Some cases had twisted hair shafts and clumped melanin. Further histological analysis is needed to determine if this is a true dysplastic syndrome or a disorder of hair cycling. We believe the latter is more likely. The symmetrical loss of hair on the caudal thighs and axillae is somewhat similar to canine pattern baldness. This disorder has three distinct clinical forms, as described by Scott et al.12 Unlike the pattern baldness reported in dachshunds, our dogs did not have any gender predilection. Clinically, none of our dogs had pinnal or facial (preauricular) involvement. Histologically, in canine pattern baldness there is moderate to severe size decrease (miniaturization) of the hair follicles – they are both shorter and thinner than normal, and the residual hair shafts are also thin. The most common finding in our study, however, was infundibular hyperkeratosis. There was a subtle decrease in follicular size in some biopsies compared with control sites; however, because morphometric examination of follicular anatomy in cases of pattern baldness and greyhound bald thigh syndrome has not been performed, strict comparisons are difficult. No distinct histopathological differences were seen between the flank and the dorsal specimens when compared with those from the thighs; however, only three biopsies from the thigh area were reviewed. Superficial pyoderma is a common finding in dogs with hyperkeratosis of the follicular infundibula, which predisposes to bacterial colonization. The presence of previous episodes of pyoderma in two dogs in this study may have contributed to the hair loss. However, when treated, normal coat condition was not achieved. In this study, we evaluated the function of the thyroid and adrenal glands, and sex hormone status. Growth hormone (GH) production was evaluated by measuring the IGF1 concentration and found to be normal in all dogs, thus a central growth hormone deficiency was unlikely. Adult-onset hyposomatotropism or GH responsive alopecia has been reported previously in a few cases,18 but it is now believed that true hyposomatotropism in adult dogs leading to alopecia is rare and that syndrome is now commonly named Alopecia X. The hair re-growth following GH supplementation was probably only an additional stimulus to the function of the hair follicle. A further study sampling nonaffected CBRs should be carried out to compare the results. The level of various hormones was measured in a specialized endocrine veterinary laboratory to assess thyroid function. This allowed us to rule out hypothy-

roidism in all our cases. One dog (no. 4) had elevated TgAA and T3 autoantibody results, suggesting that this dog has a risk of becoming hypothyroid in the future but at the time of the study it was unlikely that the hair loss in this case was related to an abnormal thyroid function. It has been reported that the CBR breed has higher prevalence of thyroid hormone autoantibodies,7,19 and the owner has therefore been advised to have the thyroid tests repeated in future for this dog. Three neutered male dogs (2, 3, 4) and four female dogs (1, 4, 7, 10) – one of which was neutered (dog 7) – had increased adrenal and sex steroid concentrations. Three female dogs (nos. 6, 8, 9) – one of which was neutered – had normal hormone concentrations despite presenting a similar pattern of hair loss to the other dogs. These hormonal findings resemble the adrenal and sex hormone abnormalities reported in Irish water spaniels.1 Two of the five intact female dogs (1, 10) had an increased concentration of progesterone and dog no. 1 had an increased concentration of androstenedione. Although the blood tests were carried out more than 2 months after the oestrus cycle (according to the owner), it cannot be ruled out that their high concentrations were the result of the diestrus phase of their cycle. The cyclic episodes of hair loss in one bitch might a cause and effect relationship between oestrus and alopecia but a larger number of affected intact bitches need to be studied to confirm this. The number of affected male dogs (intact and neutered) was insufficient to demonstrate a correlation between hair loss and male sex hormones. In contrast to human male pattern alopecia, where castration is associated with hair re-growth,20 castration in dog 5 seems to have coincided with hair loss. It is unlikely that testosterone plays a role in this syndrome. The presence of the hormonal receptors in the affected and unaffected skin in these dogs should be investigated to further evaluate this hypothesis. The results of the haematology and biochemistry tests were not indicative of classic hyperadrenocorticism or of a sex-hormone-related condition in alopecic CBRs. Furthermore, there have been no clinical signs at the time of the first examination and during the 1-year follow-up indicative of these conditions. A low-dose dexamethasone suppression test could have helped to further assess the pituitary-adrenal axis but this was considered unnecessary as the UCCRs were within normal values in all dogs. This rules out a hyperadrenocorticism-like syndrome affecting the cortisol pathway as reported in Pomeranians and miniature poodles.2 The adrenal function and the sex steroid concentrations in healthy intact and neutered CBRs should be evaluated to statistically compare the data of the affected dogs of this study. Although only four-generation pedigrees were available and considering that this is a small breed population, there is evidence suggesting a familial predisposition. The genetic basis of this disease and the mode of inheritance need to be further elucidated to eliminate this condition from the breed.

© 2005 European Society of Veterinary Dermatology, Veterinary Dermatology, 16, 39– 46

Hair loss in Chesapeake Bay retrievers The pattern of hair loss seen in CBRs has both of the clinical features seen in dogs with follicular dysplasia and pattern baldness. The histology of the affected skin of CBRs is similar and, in same cases, identical to CRFA but the history and the clinical features are markedly different. This syndrome resembles the one in the Irish water spaniel, where a multifactorial cause of hair loss was found, as previously described by one of the authors (RC).1 Interestingly, in the early 1900s an Irish water spaniel was bred to a Chesapeake Bay dog. Their progeny, highly valuable as hunting dogs, has generated many of the modern CBRs.21 It is possible that the genetic contribution from that single Irish water spaniel, which might have been a carrier of the syndrome previously reported, played a role in producing affected CBRs.

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 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: 107–22. 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 Member’s Meeting AAVD and ACVD. Maui, Hawaii, 1999: 131–7. 4. Paradis M, Sauve F, Charest J et al. Effects of moderate to severe osteoarthritis on canine thyroid function. Canadian Veterinary Journal 2003; 44: 407–12. 5. Panciera DL, MacEwen EG, Atkins CE et al. Thyroid function tests in euthyroid dogs treated with 1-thyroxine.

17. 18.

19.

20.

21.

45

American Journal of Veterinary Research 1990; 51: 22–6. Daminet S, Paradis M, Refsal KR et al. Short term influence of prednisone and phenobarbital on thyroid function in euthyroid dogs. Canadian Veterinary Journal 1999; 40: 411–15. Nachreiner RF, Refsal KR, Graham PA et al. Prevalence of serum thyroid hormone autoantibodies in dogs with clinical signs of hypothyroidism. American Journal of Veterinary Research 2002; 220: 466–71. Nachreiner RF, Refsal KR, Graham PA et al. Prevalence of autoantibodies to thyroglobulin in dogs with nonthyroidal illness. American Journal of Veterinary Research 1998; 59: 951–5. Frank LA, Hnilica KA, Rohrbach BW et al. Retrospective evaluation of sex hormones and steroid hormone intermediates in dogs with alopecia. Veterinary Dermatology 2003; 4: 91–7. Frank LA, Rohrbach BW, Bailey EM et al. Steroid hormone concentration profiles in healthy intact and neutered dogs before and after cosyntropin istration. Domestic Animal Endocrinology 2003; 24: 43–57. Randolph JF, Toomey J, Center SA et al. Use of the urine cortisol-to-creatinine ratio for monitoring dogs with pituitary-dependent hyperadrenocorticism during induction treatment with mitotane (o,p’DDD). American Journal of Veterinary Research 1998; 59: 258–61. Scott DW, Miller WH, Griffin GE. Congenital and hereditary defect. In: Muller and Kirk’s Small Animal Dermatology, 6th edn. Philadelphia: W.B. Saunders, 2001: 913–1003. Schoning PR, Cowan LA. Bald thigh syndrome of Greyhound dogs: gross and microscopic findings. Veterinary Dermatology 2000; 11: 49–51. Post K, Dignean MA, Clark EG. Hair follicle dysplasia in a Siberian husky. Journal of the American Animal Hospital Association 1988; 24: 659–62. Miller MA, Dunstan RW. Seasonal flank alopecia in boxer and Airedale terrier: 24 cases (1985–1992). Journal of the American Veterinary Medical Association 1993; 203: 1567–72. Roperto F, Cerundolo R, Restucci B et al. Colour dilution alopecia (CDA) in ten Yorkshire terriers. Veterinary Dermatology 1995; 6: 171–8. Miller WH, Scott DW. Follicular dysplasia of the Portuguese water dog. Veterinary Dermatology 1995; 6: 67–74. Bell AG, Jones BR, Scott MF. Growth hormone responsive dermatosis in three dogs. New Zealand Veterinary Journal 1993; 41: 195–9. Graham PA, Nachreiner RF, Refsal KR et al. Lymphocytic thyroiditis. In: Behrend EN, Kemppainen RJ eds. Veterinary Clinics of North America: Small Animal Practice. Philadelphia: W.B. Saunders, 2001: 915–33. Hamilton JB. Male pattern is a prerequisite and an incitant in common baldness. American Journal of Anatomy 1942; 71: 451–80. Harris AW. The Chesapeake Bay retriever. Privately printed 1946: 53–7.

Résumé Dix Chesapeake Bay retriever (CBR) présentant une chute de poils ont été sélectionnés en collaboration avec le American Chesapeake Club. Tous les chiens présentaient une perte de poils non prurigineuse, non inflammatoire, localisée, touchant les mêmes zones chez les mâles et chez les femelles. Les études hormonales ont montré une augmentation des concentrations des hormones sexuelles surrénaliennes dans sept cas. L’examen © 2005 European Society of Veterinary Dermatology, Veterinary Dermatology, 16, 39–46

46

R Cerundolo et al. histopathologique a montré une hyperkératose folliculaire et une atrophie associée à des bouchons de kératine, parfois associés à des aggrégats de mélanine dans des poils malformés. Cette étude suggère que la chute de poils dans la CBR est un syndrome dans lequel une anomalie de la production de stéroides est présente. Une prédisposition familiale semble probable et une reproduction sélective pourrait diminuer l’incidence de cette maladie.

Resumen Se seleccionaron diez perros Retriever de Chesapeake Bay (CBR) con pérdida de pelo, en colaboración con el Club Americano del Chesapeake. Todos los perros mostraban una pérdida de pelo no-prurítica, 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 histopatología reveló una hiperqueratosis y obturación folicular, atrofia folicular, y agregados ocasionales de melanina con pelos malformados. Este estudio sugiere que la pérdida de pelo en el CBR es un síndrome de la raza en el que los perros adultos jóvenes padecen una pérdida de pelo caracterizada por características histológicas inusuales y producción anormal de esteroides. Parece probable una predisposición familiar y la cría seleccionada podría 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 entzündlichen, regionalen Haarausfall, der sich bei männlichen und weiblichen Tieren auf die gleichen Körperregionen erstreckte. Hormonuntersuchungen zeigten bei sieben Fällen erhöhte adrenale und Geschlechts-Hormonkonzentrationen. Die Histopathologie zeigte follikuläre Hyperkeratose und Anschoppung, follikuläre Atrophie und gelegentliche Melaninverklumpung in malformierten Haarschäften. Diese Studie läßt vermuten, dass Haarausfall in CBR eine Rasseerkrankung ist, bei denen junge erwachsene Hunde Haarausfall haben, der durch unübliche histologische Eigenschaften und anormale Steroidproduktion charakterisiert ist. Eine familiäre Prädisposition erscheint wahrscheinlich und selektives Züchten mag das Auftreten dieser Erkrankung reduzieren.

© 2005 European Society of Veterinary Dermatology, Veterinary Dermatology, 16, 39– 46