Black Skin Disease

New Research Project by the AKC Canine Health Foundation on Black Skin Disease in Pomeranians.

Please support this very important and worthwhile research. You can make your donation through the Pomeranian Club of Canada (please provide the following information when doing so), or to the CHF directly (see contact information at the end of the project Abstract below).

Approved Grant No. 2290: 
Mapping Canine X Chromosome Linked Alopecia:
Gary Johnson, DVM, Ph.D., University of Missouri, Columbia

Lay Abstract: Many young Pomeranians develop a luxurious puppy or first hair coat which fails to shed and is not replaced by an adult coat. As the puppy coat ages it breaks off and falls out and can result in a dog that is hairless over much of its body. This disease is sometimes called black skin disease, coat funk or woolly coat. It also occurs in Keeshonden and Alaskan Malamutes. Although females can have the disease, it is much more common in males. This suggests, but does not prove, that the mutation responsible for the disease is on the X chromosome. We propose to determine if a DNA marker from the canine x chromosome associates with the disease. If so, this marker could then be used to distinguish genetically normal puppies from puppies that are likely to develop the disease. This marker could also identify female puppies that will not develop the disease but are likely to pass the disease on to the next generation.

The application was approved for funding in the amount of $18,000 pending support from clubs and/or individuals in the amount of $13,500.

Any contributions made directly to the Foundaton in support of the project will be placed in a special account reserved for this particular project. Contributions must be designated in writing (either via cover letter or in the memo section of the check) as being restricted to Grant No. 2290. Please note that CHF will match funds donated at approximately a 1:2 ratio. You can make your donation directly by contacting:

Deborah A. Lynch, Exec. Vice-President
AKC Canine Health Foundation
P O Box 37941
Raleigh, NC 27627-7941

Website: http://www.akcchf.org/
Phone: 888-682-4011 (toll free)
akcchf@aol.com

A Synopsis of the American Pomeranian Club’s Involvement with the Black Skin Disease in the Pomeranian Breed

When the American Pomeranian Club formed a Health and Genetics Committee several years ago, the committee was given "the alopecia problem" as its primary charge. Not that it is our only concern, but APC felt it was the most troublesome problem peculiar to our breed. We have chosen to officially use "Severe Hair Loss Syndrome" as its nomenclature since we don't know how many similar conditions with various causes there might be and we didn't want it to be confused with conditions other breeds call "black skin disease," such as that found in dachshunds.

We had to establish an attitude change among our breeders. Following Dr. Carmen Battaglia's advice, we offered this doctrine: Once a problem is noted generally throughout the breed, it is pointless to look backward to find "a culprit" and finger point. One must go forward and breed out the problem. Have the conviction that whatever humans have bred into a Breed has the capability of being bred out of that Breed.

The outpouring of generosity of fund raising at our last two Nationals has indicated we have advanced greatly on this open mindedness. It has been heartening that our Canadian friends have been so generous in financial support offered by the  Portage Legacy Project. The serious breed competition of the Canadians has been matched by their genuine concern for the Breed.

The American Kennel Club - Canine Health Foundation put together a grant offer combining several Nordic breeds which seem to display this problem similarly. This combined funding is going to Dr. Gary Johnson at University of Missouri to search for DNA research. Dr. Johnson is a leading DNA researcher who also is a dog fancier himself. He has established DNA breakthroughs in other breeds. He is also conducting research on epilepsy. He is particular suspicious that the Severe Hair Loss Syndrome might be located on the X chromosome.  The Canine Health Foundation matches a percentage of funds donated through the breeds' Parent Clubs. (The American Pomeranian Club is a Parent Club of the AKC.)

Finding a DNA marker would enable the breeders to conquer this problem. However, it is not the whole solution. The University of Missouri is the "DNA specialist". We also need answers about morphology and clinical treatment. Recently, APC has heard that Dr. Linda Frank is interested in addressing these concerns at the University of Tennessee .We are attempting to establish a dialogue among these two universities. Since communication does not readily exist among the scientific researchers in general, we are also trying to establish communication with researchers in Great Britain .

The APC Board has decided it was time to establish a separate charitable foundation to support all these functions more readily. Until this is complete, we will continue to funnel our financial support through the AKC Canine Health Foundation.

How can breeders personally help? The study at the University of Missouri needs Pomeranian blood samples for DNA purposes. Liz Hansen is the project coordinator at the University of Missouri . Since we still have not established whether Pom alopecia has one or more causes, she has also put together a survey which is easy to fill out. Forms and instructions for either the survey or blood samples can be downloaded from their website www.CanineGeneticDiseases.net. They need DNA samples from both affected and unaffected dogs, but related samples of three generations are especially needed.

She suggested sending in blood samples the same time that blood is drawn for heart worm testing. Instead of blood, they could also use tissue samples taken at time of any needed surgery such as spay or neutering. One advantage of participating in the study is that they would not charge for DNA testing of that individual once a test is established. The commercial rights to this test is their incentive for the research. But think of it this way, they must be committed to the possibility that they can establish this test. That is positive for our mutual purpose.

Liz Hansen can be contacted at HansenL@missouri.edu or by calling 573-884-3712

Marge Kranzfelder

APC Health & Genetics Chair

APC Board Member

APC AKC Delegate

If I can be of further assistance, I can be contacted at

kranzmar@hollinet.com or 831-623-9265.  

Click here to see what BSD looks like in an otherwise absolutely gorgeous Pomeranian

http://www.mbfonline.com/bsdauction/rocky.htm  

Alopecia X Research Project in Europe
--------------------------------------------------------

There is a new research project on Alopecia X in Europe.
Research is done by Prof. Dr. Tasso Leeb at the Institute of Genetics, University of Berne, Switzerland.

He is looking for the genetic marker for the coat loss problem Alopecia X

(also known as Black Skin Disease in Pomeranians) and has already started

collecting blood samples of affected dogs.
Prof. Dr. Leeb and his team are looking for samples of affected dogs and their close relatives.

Any participation is greatly appreciated.
The study is not restricted to Pomeranians, but will include dogs of any other affected breeds.

Information for participating is on their website:

ENGLISH:
Research project on Alopecia X

>>> Alopecia X has been described in several breeds including Keeshonds,
Pomeranians, Alaskan Malamutes, Chow Chows and Miniature Poodles. Affected
animals suffer from hair loss, which usually starts at the neck and body of
the animal, whereas the head and front legs are typically spared.
Additionally, darkening of the affected skin areas may also be observed.
Symptoms typically show up between 1-5 years of age.
We would like to investigate the genetic causes of Alopecia X. For our
research we need DNA samples from affected dogs as well as their healthy
relatives. If you would like to participate in our research project, please
follow the instructions shown below. <<<

http://www.genetics.unibe.ch/content/rubrik/alopecia_x/index_eng.html

The balance of this page is comprised of several papers on this topic. Most of the articles are by Veterinarians, but there are also articles by others knowledgeable in the Pomeranian breed, or on this topic. If you know of an article that could aid our understanding of this topic, we'd love to hear from you. Thanks to Laurie Kinsman (Pomeranian breeder and member of the PCOC), for agreeing to type the articles that are reproduced here. Just click on any of the titles below to view that article.

List of Titles

Growth Hormone-Responsive Alopecia in Dogs

by Clinon D. Lothrop Jr., DVM, PhD; and Lynn P. Schmeltrel, DMV

Canine Growth Hormone-Responsive Dermatitis

by Clinon D. Lothrop Jr., DVM, PhD

Malassezia Pachydermatitis and Associated Dermatitis:

One Cause of Severe Hair Loss

by Charlotte Creed

Pathophysiology of Canine Growth Hormone Responsive Alopecia

by Clinton D. Lothrop, Jr., DVM, PhD

Virkon Germicidal Skin Cleanser proven effective against Malassezia Pachydermatis and Staphylococcus Intermedius

source: www.antecint.co.uk

More on Black Skin Disease

Article/Letters as  printed by the PCOC in the September 1997 Club Newsletter  

Growth Hormone-Responsive Alopecia in Dogs

ABSOLUTE GROWTH HORMONE DEFICIENCY IS NOT PRESENT IN ALL CASES

Reprinted from Veterinary Medicine Report St. Louis Vol. 2, No. 1, pp. 81 & 83, Jan.,1990 (Copyright ã 1990, by The C.V. Mosby Company) 

Clinton D. Lothrop Jr., DVM, PhD, Associate Professor, Department of Environmental Practice, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee.

Lynn P. Schmeltrel, DMV, Diplomate, ACVD, Associate Professor of Dermatology, Department of Urban Studies, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee

Growth hormone-responsive alopecia of adult dogs is apparently a syndrome of multiple causes.  A true growth hormone deficiency is not present in all dogs with this disease.  Adrenal and gonadal steroid hormones and their biosynthetic precursors contribute to hair loss seen in dogs with this syndrome.  The exact cause(s) of this syndrome are likely to differ in the various breeds affected and must be defined before appropriate and rational treatment modalities can be developed.

Canine GH-responsive alopecia is an acquired alopecia of adult dogs.^1-5  Its primary characteristics are a loss of primary hairs with retention of secondary hairs.  This disease is seen most frequently in the Pomeranian, poodle, chow chow, samoyed, keeshonden, and American water spaniel breeds.  The alopecia can occur in dogs of any age but often develops at puberty.  Dogs with this syndrome are not dwarfed in stature, do not have signs of systemic illness , and have normal thyroid and adrenal function tests.  There is no proof of genetic inheritance of this syndrome, but the predisposition of certain breeds suggests hereditary influences.

Siegel⁶ first described canine GH-responsive alopecia in 1977.  Siegel coined the term pseudo-Cushing’s syndrome to describe this disorder because the alopecia was similar to that seen in dogs that had Cushing’s syndrome.  The alopecia also resembles that seen with pituitary dwarfs, which may account for the initial suspicion of adult-onset GH deficiency in dogs with trunical alopecia but normal thyroid and adrenal function.

GH-responsive alopecia can be diagnosed by measuring serum GH concentrations before and after stimulation with an a-adrenergic agonist (clonidine, xylazine) or GH-releasing factor.^1,7 The absence of a significant increase in serum GH concentration suggest GH-responsive alopecia. Treatment is by subcutaneous administration of human, porcine, or bovine GH for 4 to 6 weeks.^1,8

Ninety-five dogs with possible adult-onset GH-responsive alopecia that had normal adrenal and thyroid function were evaluated with a GH responsive test (Table 1).  Only 63 of 95 dogs had a decreased GH response (Table 1).¹   The 32 dogs with a normal GH response had the typical moderate to severe trunical alopecia and hyperpigmentation, as did the 63 dogs with a decreased GH response.  The normal GH response in some dogs suggests that a GH deficiency is not always associated with this dermatitis.  Furthermore, serum levels of somatomedin C, which is produced in response to GH and should be deceased in dogs with true GH deficiency, were not decreased in dogs with an abnormal GH response.¹

Castration has corrected the alopecia in some intact male dogs, even though reproductive hormone levels and testicular histopathologic findings are not abnormal.  Other male dogs (both intact and castrate) have responded, albeit often temporarily, to testosterone replacement.  Thus we conclude that, although dogs may respond to GH supplementation with hair regrowth, an absolute GH deficiency is not present in all dogs with this syndrome.

The Pomeranian breed is reported to have an increased incidence of GH-responsive alopecia.  However, both normal Pomeranians and Pomeranians with GH-responsive alopecia have a decreased GH response to the a-adrenergic agonist xylazine and to GH-releasing factor.⁹ Since normal and affected Pomeranians have decreased GH levels relative to other breeds of dogs, the role of GH deficiency in affected Pomeranians is not clear.  Furthermore, affected Pomeranians apparently have a non-classic “late-onset” deficiency of the adrenal enzyme 21-hydrozylase.  The partial deficiency of 21-hydroxylase causes an overproduction of steroid presursors such as progesterone, 17-hydorxyprogrestrone, androsternedlone, and dehydrooephandrosterone sulfate.⁹  Elevated serum adrenal androgens have been associated with male pattern baldness in women.^10,11  The elevated adrenal progestins and androgens may contribute to the alopecia seen in affected Pomeranians.  The adrenolytic agent o.p. DDD has to date been used successfully to treat at least two Pomeranians with this syndrome, confirming a role for the adrenal gland in the pathogensis of this syndrome in Pomeranians.

In summary, GH-responsive alopecia is an endocrine alopecia of adult dogs of unknown cause.  Although an absolute GH deficiency may be present in some dogs with this syndrome, it is unlikely to be the primary cause of hair loss in some breeds.  More likely, multiple causes result in a similar clinical syndrome.

References:

1. Lothrop, CD Jr., Pathophysiology of growth hormone responsive dermatosis. Compend Cont Educ Pract Vet 1988:10:1346-1352.

2. Eigenmann JE, Patterson DF. Growth hormone deficiency in the mature dog. J Am Anim Hosp Assoc 1984:20:741
3. Parker Scott DW. Growth hormone-responsive alopecia in the mature dog: a discussion of 13 cases. J Am Anim Hosp Assoc 1986:22:467.
4. Scott DW, Walton DK. Hyposomatotropism in the mature dog: a discussion of 22 cases. J Am Anim Hosp Assoc 1986:22:67.
5. Campbell KL. Growth hormone-related disorders in dogs. Compend Cont Educ Pract Vet 1988:10(4):477-482.
6. Siegel ET. Endocrine diseases of the dog. Philadelphia: Lea & Febiger, 1977
7. Hampshire J. Altszuler N. Clonidine or zylazine as provocative tests for growth hormone secretion in the dog. Am J Vet Res 1981:42:1073
8. Eigenmann JE. Growth hormone-deficient disorders associated with alopecia in the dog. In: Kirk RW, ed. Current veterinary therapy  IX. Philadelphia: WB Saunders Co., 1966:1015.
9. Schmeltzel LP, Lothrop CD Jr. Evaluation of hormonal abnormalities in normal coated Pomeranians and Pomeranians with growth hormone responsive dermatosis. Proceedings AAVD, 1988:29-30
10. Nelson D. The acirenal cortex: physiological function and disease. In: Smith LH, ed. Major problems in internal medicine. Vol. XVII. Philadelphia: WB Saunders Co., 1980.
11. Kasick JM, Bergfeid WF, Steck WD, etal. Adrenal androgenic female-pattern alopecia: sex hormones and the balding woman. Cleve Clin Q 1983:50:111-122.

Back to List of Titles

Canine Growth Hormone-Responsive Dermatitis

Clinton D. Lothrop Jr., DVM, PhD, Knoxville, Tennessee.

Canine growth hormone-responsive dermatosis, first described by Siegel in 1977, is a rare endocrine alopecia of mature dogs.  The primary clinical features of this syndrome are bilaterally symmetric alopecia and hyperpigmentation occurring mainly on the trunk, caudal thighs, collar area, pinna, and tail, while sparing the head and legs.  The alopecia is characterized y a retention of the secondary hairs (undercoat) with a loss of primary hairs (guard).  Siegel coined the term pseudo-Cushing’s syndrome to describe this disorder, because the alopecia resembles that in Cushing’s syndrome.  However, dogs with uncomplicated growth hormone-responsive dermatosis have normal hemograms, serum chemistries, urinalyses, and normal results of adrenal and thyroid function tests.  Skin biopsies from dogs with growth hormone-responsive dermatosis are characterized by histopathologic changes consistent with an endocrine dermatosis; orthokeratotic epidermal thinning, follicular ketarosis and telogenization, and subaceous gland atrophy.  Decreased dermal elastin content has been suggested to be a histopatholgic abnormality specific for growth hormone-responsive dermatosis but is routinely seen only in dogs that have clinical signs for at least 2 years.  In addition, a decreased dermal elastin content can rarely be seen in other catabolic endocrine skin disorders, such as diabetes mellitus and hyperadrenocorticism.

Growth hormone-responsive dermatosis occurs predominantly in Pomeranians, chow chow, poodle, water spaniel, keeshond, and Samoyed breeds but can occur in any breed of dog.  The age of onset of growth hormone-responsive dermatosis is most commonly between 1 and 2 years but can occur at any age.  There appears to be an increased incidence in male dogs of certain breeds.  The hallmark of growth hormone-responsive is the correction of integumentary abnormalities with growth hormone replacement.  Growth hormone-responsive dermatosis has been suggested to be due to growth hormone deficiency occurring in the adult dog, but the pathogenesis of this syndrome has yet to be defined.  Necropsy results for two dogs with grown hormone-responsive dermatosis showed moderate atrophy of the pituitary gland in one case.  There is no proof of a genetic inheritance of this syndrome, but the predisposition of certain breeds suggests there may be hereditary influences.

Endocrine alopecia and dwarfism occur with growth hormone deficiency in the immature dog.  Pituitary dwarfism occurs most commonly in the German shepherd and Carnelian Bear Dogs and appears to be inherited as an autosomal recessive trait.  This disorder differs from adult-onset growth hormone responsive dermatosis in that partial to complete deficiencies of adrenocorticotropin, thyrotropin, and gonadotropins are found along with the somatotropin deficiency.  Pituitary dwarfs often appear normal until 2 or 3 months of age, at which time failure to grow is noticed.  The hair coat often remains short because of inadequate development of primary hairs.  The typical truncal alopecia and hyperpigmentation develop in dwarf dogs with growth hormone deficiency.  Most dwarf dogs have a colloid-filled pituitary cyst at necropsy, with secondary changes in other endocrine glands.  The alopecia of dwarf dogs will respond to growth hormone supplementation, but longitudinal bone growth and increased stature do not occur owing to closure of the growth plates.  If concurrent hypothyroidism is present, thyroxine replacement is necessary to obtain optimal results.  Although the endocrine alopecia in dwarf dogs and dogs with adult-onset growth hormone-responsive dematosis responds to growth hormone supplementation, the presence of multiple pituitary abnormalities in dwarf dogs and differences in pituitary histopathology in these two syndromes suggests that the pathogenesis of these syndromes may be different. 

DIAGNOSIS OF GROWTH HORMONE DEFICIENCY

The diagnosis of growth hormone deficiency can be confirmed by measurement of serum or plasma growth hormone.  Measurement of a basal growth hormone concentration is inadequate to correctly diagnose growth hormone deficiency, since many normal dogs have a low basal growth hormone concentration.  Therefore, a growth hormone response test should be performed using the alpha-adrenergic agonist clonidine (10mg/kg).  These agents stimulate growth hormone release by inducing production of endogenous growth hormone releasing factor (GRF).  Alternatively, human GRF (1 to 5 mg/kg) can be used to stimulate growth hormone production.  To perform a growth hormone response test, 2 to 4 ml of blood should be collected before at 15, 30, 45, 60 and 120 min after intravenous administration of either clonidine, xylazine, or CGR.  After collection, the blood should be promptly centrifuged and the plasma (EDTA) or serum frozen at -20°C until assayed for growth hormone.  Homologous canine growth hormone radioimmunoassays are used to determine the plasma or serum growth hormone concentration.  The absence of a significant increase in the plasma or serum growth hormone concentration is consistent with the diagnosis of growth hormone deficiency.

Both clonidine and xylazine are potent hypotensive agents and should be used cautiously.  Side effects, at the recommended doses, range from mild drowsiness and bradycardia to complete collapse, and last from 15 to 60 min.  If necessary, atropine can be used to correct the bradycardia and the alpha-adrenergic antagonists phentolamine or yohimbine can be used to antagonize the hypotensive and hyperadrenocorticism effects of clonidine and xylazine.  Hypothyroidism and hyperadrenocorticism should be ruled out with appropriate thyroid and adrenal function tests prior to performing a growth hormone response test in a dog with suspected adult-onset growth hormone-responsive dermatosis, since these disorders can potentially induce a reversible growth hormone deficiency.

CLINICAL FINDINGS IN ADULT-ONSET GROWTH HORMONE-RESPONSIVE DERMATAOSIS

A growth hormone response test (using either xylazine or GRF as a provocative stimulus) was eveluated in 95 dogs with suspected adult-onset growth hormone-responsive dermatosis.  All animals were in apparent normal health, except for the typical moderate to severe truncal alopecia and hyperpigmentation.  Thyroid and adrenal function test results were determined to be normal in each animal.  A complete or partial lack of a growth hormone response was observed in 63 of the 95 animals (Table 1).  A total of 32 breeds of dogs were represented in the 95 animals suspected of having adult-onset growth hormone-responsive dermatosis.  Several breeds of dogs appeared to be predisposed to adult-onset growth hormone-responsive dermatosis, including the chow chow, poodle, Pomeranian, water spaniel, keeshond, and Samoyed.

Table 1. Reproductive Status and Growth Hormone Levels in 95 Dogs With Suspected Growth Hormone-Responsive Dermatosis