Alopecia

 

Alopecia and Coat Loss in the Keeshond

Background

In a coated breed most owners strive to ensure their dogs have that perfect coat. Today with more emphasis than ever on the amount of coat dogs have it is of concern to owners when their dogs suddenly start to loose coat and even develop patches of alopecia.

Most Keeshond owners are aware of cases of dogs and bitches loosing areas of coat from the thighs. I can remember over 30 years ago being told that the “cure all” was Bob Grass Skincure. This traditional product contains amongst other ingredients sulphur, known for its beneficial effect on skin disorders. There have also been other traditional suggestions such as castrating a dog or allowing a bitch to have a litter. If the coat problem resolved people concluded the “treatment” had been the cause. There have however been cases of dogs re-growing areas of alopecia with no treatment via surgery or medication.

It is generally understood that coat condition and growth in an otherwise healthy dog is due to some kind of hormone imbalance but it is not fully understood why.

There appears to be a greater tendency in certain Spitz breeds. Many owners will immediately think of thyroid deficiency and may request their vet to carry out a simple test for thyroid function. If the result is within the normal range the owner and vet are often left wondering what to do next.

In 1998 a study was commenced by, veterinary surgeons working in the Department of Dermatology at the Royal Veterinary College. The study set out to look at patterns of coat loss in Spitz breeds and sought to gain help from breed clubs of Chows, Samoyeds, Pomeranians and Keeshonds. A number of breeds appear to be susceptible to patterns of coat loss and the department has also carried out studies with Irish Water Spaniels. Breed Clubs were invited to become involved and individual owners requested to submit dogs showing patterns of coat loss or poor coat growth to the department of dermatology at the RVC North Mymms site.

Typical symptoms are thinning of hair or total alopecia in certain parts of the dog’s body. Alopecia is generally bilateral (appearing equally on both sides of the body) and affecting the lateral neck, (area on both sides of the throat), rump area near root of tail and along the area of the second thigh on back legs. The areas of coat loss around the neck are often thought to be due to friction from a badly fitting collar, as they appear to be where the collar lies. In fact the collar generally has nothing to do with the problem. Coat texture in these areas is often harsher than the remainder of the body and has a tendency to break readily when brushed. There is generally no sign of pruritus (itching) or lesions of the skin of affected dogs. In Keeshonds this type of coat loss appears to be more common in males although bitches can show the same symptoms.

There have been cases where an affected dog has, for no apparent reason regrown hair on the alopecic areas and where this has occurred the hyperpigmentation appears to resolve itself. Alopecia may or may not reoccur.

 

The Survey Methods

Owners of dogs participating in the survey were asked to complete a questionnaire explaining when the coat loss commenced and any links to times of year etc. An outline of a Spitz was provided to illustrate the areas of coat loss. Where possible owners were also requested to send photos to illustrate the dogs coat loss. Some owners visited the Royal Veterinary College with their dogs to enable a range of tests be carried out and others were tested by their own vets using the set protocol provided by the survey. Blood samples were taken and a standard haematology and biochemistry assay completed.

An ACTH test was also carried out testing for cortisol and 17 OHP pre and post stimulation. Dogs were tested for thyroid function with T4 and TSH. Several skin sections were collected both from areas affected by the alopecia and hyperpigmentation and also from an unaffected area to act as a control.

A series of urine samples were subsequently collected by owners and sent to a specialist laboratory for analysis.

During the latter part of 2000 a food study was carried out on a number of dogs as diet has been found to have an effect in others breeds, notably the Irish Water Spaniel. Wafcol provided supplies of their fish and corn complete diet for owners to take part in a fixed period food trial.

Results

Oestradiol (oestrogen) levels were well above the normal reference range in all dogs. Testosterone was within normal range although there was a considerable variation. The TSH levels within these samples were also within normal ranges. T4 levels were within the normal reference range for most. No dogs were hypothyroid.

Urine analysis showed no abnormalities.

All the tested dogs showed elevated 17 OHP levels post stimulation.

The food trial did not show any significant improvement. There was slight improvement in one dog only. Several owners reported having difficulty encouraging their dogs to eat the food.

Conclusions

The condition is referred to as Alopecia X. (Adrenal Hyperplasia Syndrome) Onset has been found to occur at any age and does appear to be more common in “plush-coated” breeds such as the Spitz breeds.

It was concluded that the hormonal results of all the dogs showed an increased level of 17 OHP post ACTH stimulation and an increased level of oestradiol (oestrogen). This is a common finding in dogs with this disease. This type of coat loss is now thought to be due to abnormal steriodogenesis (a slightly abnormal adrenal gland function in the pathway of steroid formation such as cortisol). It is not known to what extent the condition in the different breeds is caused by the same hormonal imbalances as the tests showed different patterns in the breeds within the survey. There appears to be a difference between the hormonal imbalance in the Keeshonds and that of other breeds. It is possible that Keeshonds have a mild form of the alopecia that affects Irish Water Spaniels, Miniature Poodles and Pomeranians.

Where do we go next?

A drug thought to be suitable for correcting this imbalance has been identified and received its UK licence last year. Trilostane is licensed for use in Cushings disease but has also shown encouraging results when used as a therapy for coat loss.

The drug is considered to be extremely safe to use and to date trials have been carried out on Pomeranians and Miniature Poodles. Results have been encouraging with 90% efficacy in the trial (Cerundolo, personal communication). The drug needs to be balanced carefully and it can take several months to obtain the optimal balance.

The initial investigations were funded via a Kennel Club grant to the RVC and this has now ceased. The drug company provided medication for the trial on Pomeranians and Miniature Poodles. For the time being at least any continuation of the study is “on hold”. It is hoped that it will be possible to recommence work with Keeshonds at some time.

In the meantime it is important to remember that this disease is purely cosmetic and affected dogs are healthy in every other respect.

Acknowledgement

I would like to thank Rosario Cerundolo D.V.M. Cert. VD, Dipl. ECVD, MRCVS for his advice and support in the writing of this article, and also for involving Keeshonds in the Alopecia X study.

References

Cerundolo R (1999) “Symmetrical alopecia in the dog”: In Practice,21: P 350 -359  Cerundolo R, (2000) “Alopecia associated with abnormal steriodogenesis in dogs”, Continuing Professional Development – Veterinary Medicine2: P 100-104,
Cerundolo R, Lloyd DH, Pidduck HG (1999) “Studies on the inheritance of hair loss in the Irish Water Spaniel” Vet Rec. Nov 6; 145(19): P 542- 4
Cerundolo R , Lloyd D.H., McNeil P.H., Evans H, (2000) “An analysis of factors underlying hypotrichosis and alopecia in Irish Water Spaniels in the United Kingdom” Vet Dermatology;11 P 107-122 August 2002

© Jane Saunders – August 2002

  

Alopecia X – a way forward with Trilostane drug therapy.

  

Background to the study

It is hard to believe that it was back in 1999 that I first became involved with the Alopecia X survey of Spitz breeds in the UK. At the time Dr Rosario Cerundolo was working at the Royal Veterinary College in the UK. As I reported in my 2002 paper, there had been evidence of coat loss in the Keeshond for many years with a variety of anecdotal ideas on how to resolve it.

In recent years coat loss has become more evident and a familial pattern has become apparent. Whilst it is comforting for the owner of an affected dog to be informed that the condition is basically a cosmetic one, with the affected animal being otherwise healthy, most owners would prefer their dogs coat   to  re-grow.

At the time of writing the previous paper the researchers had identified the drug trilostane as being potentially suitable for correcting the imbalance. The drug produced by Arnolds Veterinary Products (now called: Dechra Pharmaceuticals PLC) had recently received its UK licence for the treatment of Cushing’s syndrome. (Hyperadrenocorticism) The trial had very encouraging results and the following paper summarises the research paper produced to report on the trial. (Cerundolo, R, Lloyd DH., Persechino A, Evans H & Cauvin A – 2004)

The Trilostane Study

The original study had shown that a number of Spitz breeds, including the Keeshond showed a predisposition to develop a form of coat loss known as Alopecia X. Contrary to some popularly held thought that X means that it is sex linked, this has not been shown to be the case. The use of the letter X in describing this form of alopecia in dogs is to indicate that there is no obvious cause.

Alopecia X is a form of adult onset alopecia and it is known both clinically and commonly by a wide variety of names, including Black Skin Disease, Coat Funk and The Disease. The clinical names merely reflect the descriptions of the various endocrine findings and/or therapeutic responses to various therapeutic treatments such as castration. Nordic breeds have been shown to be particularly affected along with the Miniature Poodle.

The drug trilostane has been reported to be a competitive inhibitor of the conversion of pregnenolone, 17-OHP hydroxypregnenolone, dehydroepiandrosterone and androstenediol by blocking the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD).

Alopecia X is assumed to be an endocrine disorder and testing has confirmed that affected animals show an increased blood concentration of 17-OHP. Previous studies have shown alopecic dogs have a slight increase in cortisol production.

The researchers hypothesized that trilostane could promote hair re-growth by modulating adrenal steroidogenesis, down regulating the levels of 17-OHP and cortisol through inhibition of the 3β-HSD enzyme.

Sixteen Pomeranians and eight Miniature Poodles presenting with clinical signs of Alopecia X, elevated blood concentrations of 17-hydroxyprogesterone post stimulation with adrenocorticotropic hormone and increased urinary cortisol/creatinine ratios were treated with trilostane once or twice daily at a mean dose of 10.85 mg kg-1 day-1. The researchers recruited animals identified with the condition from the previous UK study (Cerundolo and Lloyd). All had various degrees of coat loss that had been identified to be consistent with the diagnosis of Alopecia X.

The 16 Pomeranians consisted of 7 neutered females, one female and 8 males. The 8 Miniature Poodles were one neutered female, one female and 6 males.

At the first consultation the ages ranged from 2 – 9 years and the age of onset varied from 1½ – 8 years.

Breed Age of
onset
mean age
of onset
Pomeranian 1½ – 8 years 4.45 years
Miniature Poodle 4 – 8 years 5.62 years

Fig 1: Age data of animals included in the study

All affected dogs showed varying degrees of truncal alopecia.

Re-examination

Dogs were re-examined after 10 days and 4 weeks of treatment, and also after 12 weeks and in some cases 1 year. Re-examination was carried out in the morning and a full battery of haematological, biochemical and urine analysis were carried out to assess the animals’ health status. An ACTH stimulation test was also performed.

The animals’ progress was subsequently reviewed approximately every 6 months. If not response to treatment was observed after two months, the dose of trilostane was doubled with administration once or twice a day.

Clinical Findings

The treatment of animals showing clinical signs of Alopecia X resulted in complete hair re-growth in 14 of the 16 Pomeranians, representing an 80% success rate. The success rate among the 8 poodles was 100%.

Hair re-growth in all but two Pomeranians occurred in 4 – 8 weeks. Two Pomeranians had no hair re-growth after 6 months of therapy. The hair type in Pomeranians was initially woolly but normal primary and secondary coat appeared later. The coat of white Miniature Poodles grew back light brown, especially on the limbs. However this subsequently became white again. There was no significant difference in the dose per kg per day of the two breeds.

Follow-up

The treated dogs were followed up over a period of 6 – 33 months with follow up either by the researchers or through their referring veterinarians. When full re-growth was achieved two Pomeranians had their doses reduced to a maintenance dose of 20mg (thrice weekly). There was no reoccurrence of coat loss.

Various patterns of medication were given to individual dogs as needed. Two Miniature Poodles eventually had trilostane withdrawn with no reoccurrence of coat loss.

Discussion

The pathogenesis of Alopecia X has been the subject of considerable debate and response to treatment has often been used to support the different theories that have been put forward. In many cases neutering has been the treatment of choice in male dogs with partial or complete hair re-growth occurring within 3 – 4 months. Only one of the miniature poodles in the study had been castrated but in this case coat loss had occurred sometime later. A variety of drugs have been used over recent years with inconsistent results.

The authors confirmed that abnormal steroidogenesis is present in affected dogs as they have not only an increased serum 17-OHP concentration but also mildly increased cortisol production and excretion, resembling natural pituitary-dependant hyperadrenocortism (Cushing’s syndrome). The authors postulated that this is a breed associated mild form or a variant of pituitary-dependent hyperadrenocorticism.

The study showed that trilostane is a safe and valid choice for the treatment of Alopecia X. Its effect seems to be dose responsive with dogs responding at daily doses from less than 6 to over 23 mg kg-1. Side effects associated with adrenal function were not observed in treated dogs and routine biochemical investigations did not reveal any electrolyte abnormality.

It was concluded that further studies are needed to establish the dose requirements more accurately. The study showed that there is scope for varying the dosage when once a good clinical response has been achieved. This will be of benefit to owners as it will reduce the cost of maintenance therapy.  It is possible that Trilostane works in reversing hair loss by initiating new hair growth of anagen hairs. Pulse therapy might be effective after initial re-growth.

Two Miniature poodles continued to re-grow coat despite being withdrawn from the study and this is unexplained. Two Pomeranians failed to re-grow coat after 6 months of therapy. The owner then decided to discontinue the treatment. It is not known why the treatment failed to help these two cases, but it is possible that they may have needed an increased dose. White miniature poodles had a brown colouration on newly grown coat, but this subsequently turned white. The cause of this is thought to be an accumulation of melanin in the hair follicle bulbs.

A previous study indicates that trilostane does not react with any of the sex steroid receptors; although a possible peripheral activity on oestrogen receptors has recently been reported. It is questionable whether the hair re-growth achieved in the patients is related to peripheral activity of trilostane (e.g. by blocking the oestrogen receptors in the hair follicle) but further studies are necessary to look at the hormonal receptor distribution in dogs with Alopecia X and the effect of Trilostane on the sex hormone and corticosteroid receptors at the level of the hair follicles in dogs.

Two Pomeranians died during the follow-up period but there was nothing to suggest that Trilostane therapy had any effect on this. Both dogs had heart murmurs but their referring veterinarians had not felt they needed any medication. There is a possibility that Trilostane might have contributed to alteration of cardiac function and it is advisable any dogs with cardiac problems are closely monitored if they are being considered for Trilostane therapy.

How can this research benefit Keeshonds?

The original study in the UK did include a number of Keeshonds and the findings were consistent with those of the Pomeranian. Limited funding at the time of the Trilostane study prevented more breeds being included.

                                                                                                      

         

  Fig 2: Coat loss on lateral neck and on thighs

How can we learn more about this condition in our breed?

In order to start a clinical trial a number of dogs affected with Alopecia X will be needed. If you have a Keeshond with coat loss your help would be greatly appreciated. There would be no need to travel to Philadelphia as it would be possible for diagnostic tests and treatment regimes to be carried out via your own veterinarian.

If you would like to help this important research for our breed, please contact Dr Rosario Cerundolo at the address given at the end of this article.

Acknowledgement

I would like to thank Rosario Cerundolo D.V.M. Cert. VD, Dip ECVD, MRCVS for allowing me access to the paper on the trilostane study. I am also grateful to Rosario for his advice and support in the writing of this article.

Dr. Rosario Cerundolo is Honorary Professor of Veterinary Dermatology and at the time of writing was Associate Professor of Veterinary Demratology at the University of Pennsylvania, Department of Veterinary Medicine.

References

Cerundolo, R, Lloyd DH., Persechino A, Evans H & Cauvin A (2004) Treatment of canine Alopecia X with trilostane. Veterinary Dermatology 15 (5), 285-293.
Cerundolo R, Lloyd DH, Vaessen M et al. Alopecia in Pomeranians and Miniature Poodles is associated with abnormal pituitary-adrenal function. The Veterinary Record (in press).
Leone F., Cerundolo R., Vercelli A., Lloyd D.H. The use of trilostane for the treatment of adult-onset alopecia (“coat funk”) in Alaskan malamutes. Journal of the American Animal Hospital Association (in press).
© Jane Saunders – June 2005

 

Rosario Cerundolo DVM, Cert. VD, Dip. ECVD, MRCVS

  Qualifications

DVM, Cert. VD, Dip. ECVD, MRCVS

RCVS Specialist in Veterinary Dermatology
Royal College of Veterinary Surgeon (UK)
Diplomate of the European College of Veterinary Dermatology

Correspondence e-Mail:  Rosario Cerundolo  

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