Poor coats and how to grow hair (Proceedings)

Poor hair coats and alopecia that are not a result of inflammation or pruritus and are symmetric or involve much of the body most commonly reflect a disorder of hair growth that is metabolically or genetically related. In general the disorders will fit into one of four categories.

Nutritional/Metabolic

Inadequate intake or utilization such as results from malabsorption or liver disease

     • protein,

     • fatty acids

     • zinc

     • vit A

     • Endocrine

          o Hyperglucocorticism

          – Natural pituitary dependent, adrenal tumor

          – Iatrogenic

          o Hypothyroidism

          o Hyperestrogenism

          – Gondal, iatrogenic, neoplasia, adrenal

          o Hyperprogesteronism

          – Gondal, iatrogenic, neoplasia adrenal

     • Follicular dysplasia

     • Endocrine Modulated

          – Alopecia X–Adrenal syndrome-Atypical cushings

          – Castration responsive –

          – Canine cyclic flank alopecia

          – Siberian husky and Malamute follicular dysplasia

          – Irish Water Spaniels

          – Chesapeake Bay retriever (CBRS)

     • Non Endocrine Modulated

          o Abnormalities in Melanin transfer or production

          – Color dilution alopecia (CDA)

          – Black hair follicle dysplasia (BHFD)

Congenital Malformation of hairs

          – Hairless breeds

          – Congenital hypotrichosis

          – X linked ectodermal dysplasia

          o Post Clipping Alopecia

          o Follicular lipidosis of rottweilers

          o Pattern alopecia

          o Pinnal alopecia

          – Pinnal alopecia

          – Caudal pinnal, ventral and thigh alopecia

          – Non-classic, curly coated retriever, American water spaniel and Portuguese water dogs

     • Keratinization/epithelialization

     • Primary idiopathic seborrhea

     • Sebaceous adenitis

Based on the above classification system it is important with these cases that dogs are maintained on good diets and there is no evidence of gi disease or malabsorption syndromes. Iatrogenic steroidal hormone exposure either systemic or topical(including touching or licking humans with topical therapies) should be ruled out historically. Any evidence of metabolic or behavioral changes suggests disease from group 1 and 2 as dogs with diseases in groups 3 and 4 tend to be healthy normal dogs other than their skin changes. Routine chemistry tests and thyroid tests should be run. If abnormal then treating the cause of the abnormalities is the first step. In cases with elevated serum alkaline phosphatase enzymes then cushings disease needs to be ruled out. If cushings is not present then adrenal sex hormone and atypical cushings disease are main differentials for the elevated alkaline phosphatase if the haircoat changes appear hormonal. Spaying and castrating dogs still intact is generally recommended in these cases in case there is a gonadal source of steroidal hormones. When all the preceding is normal in spayed or castrated dogs then it is even more likely one is dealing with category 3 and 4 in which cases a biopsy is the most informative test to run. The other test to perform is the acth stimulation test with adrenal sex hormones. This has become a controversial test as so far successful therapy has not been shown to decrease with changes in abnormal sex hormones.[1, 2] In addition there are other problems listed for successful interrpreation of sex hormones effect on the skin.

     • Problems for complete interpreteation of sex hormone tests

     • Assays are very specific for each hormone

     • Total serum levels usually measured

     • Free hormone levels may be different depending on carrier protein levels

     • Numerous metabolites for each class of hormones occur

     • Different metabolites vary in ability to stimulate receptors

     • Numbers of receptors may vary from site to site

     • Also need information on breed, coat type and age variations

     • Other hormones may have some affinity and activity on receptors, ie androgens stimulate estrogen receptors in males

     • Other hormones, cytokines, chemokines may affect expression of activity on cutaneous targets

     • Conversion to other hormones at target tissue can occur

     • Fluctuation in levels occurs (photoperiod, estral cycle)

     • Showing abnormal level not prove cause unless see response to altering that level

     • Degree of response may also be important___________?

In general dogs in the last two categories are unlikely to have a normal coat return but should be on good quality protein and high fatty acid diets. When possible specific therapies for any of the diseases diagnosed should be instituted. For most of these syndromes and especially the disorders referred to as alopecia X, atypical cushings or adrenal hyperplasia syndrome then the following treatments have all been reported effective in some cases.

Drug therapies that affect sex hormone levels and are reported to help dogs in category 3 include:

     • Melatonin decreases estradiol, 17-hdroxyprogesterone in males and estradiol, testosterone and dehydroepiandrosterone in females.

     • Implants available at www.MELATEK.net dogs under 25lbs one 8 mg implant, 25-50 lbs one 12mg implant , >50 lbs one 18mg implant

     • Phytoestrogens (isoflavones, lignans, genistein) inhibit 3-beta hydroxysteroid dehydrogenase. Lignans and genistein may decrease aromatase enzyme in some cells.

     • Flax seed hull not oil is a good source of secoisolariciresinol diglucoside lignin (SDG flax hull lignin) and is dosed at 1mg/lb q24h of SDG.

     • Ketoconazole decreases androgens and increases progestins.

     • Goserelin, an anti-gonadotropic drug lowers estradiol and progesterone.

     • Lysodren reduces the cortisol but also sex hormone production from the zona reticularis of the adrenal gland and many dogs with congenital hyperplasia-like syndrome as well as other alopecia X cases have clinically responded to this drug.

     • Trilostane which also decreases steroid production from the adrenal gland has been shown to be very effective in growing hair in the Pomeranians and poodles with what is called alopecia X.

Treatment comments

Melatonin is often initially recommended for pattern baldness, seasonal flank alopecia and alopecia X due to its safety, easy accessibility and low cost. In alopecia X it only seems effective in one third of the cases. One recent study reported 40% respond to melatonin therapy with some hair growth.[4] Melatonin is dosed several ways and most commonly 3mg q12h in dogs under 15kg and 6mg q12h in dogs over 15kg. However 1.0 –1.3mg/kg q12h may have higher efficacy

When estrogens are elevated then ground flax seed as a source of lignans is tried for 4-8 weeks and alone has little apparent benefit. It is also used in conjunction with other drugs so it is difficult to judge its efficacy but since it is realatively safe and also a good source for omega 3 fatty acids it is still utilized.

Trilostane, a drug that blocks adrenal steroid hormone synthesis via competitive inhibition of 3 Beta-hydroxysteroid dehydrogenase enzymes. Dogs with pituitary dependent cushings do have decreased cortisol but no change in the 17 OH Progesterone levels and the authors suggest there maybe other enzymes affected in dogs than what is classically described.[5] The enzyme system mediates the conversion of pregnenolone to progesterone in the adrenal glands. Pomeranians and Miniature poodles, trilostane was shown to be very effective where 22/24 cases in Pomeranians and all poodles responded.[6] Dosed initially at 1mg/kg q12h and then adjusted based on post acth cortisol levels. Some cases may not respond unless high dose even 10mg/kg per day are reached. Over time some cases that have grown hair may have there dose tapered to once daily or even eod.

O, P-DDD (Lysodren, Mitotane) has been most effective for the author in treating alopecia x cases. An induction phase of Lysodren at 15-25mg/kg/q24h is used for the first 3-5days. A post ACTH cortisol level between 5-7ug/dl (50-70ng/ml) is desired following induction and also the goal of maintenance. Maintenance doses are approximately 25mg/kg q 7d –14d however the dose is adjusted based on post ACTH cortisol levels.

References

Frank, L., K. Hnilica, and J. Oliver, Adrenal steroid hormone concentrations in dogs with hair cycle arrest (Alopecia X) before and during treatment with melatonin and mitotane. Vet Dermatol, 2004. 15(5): p. 278-284.

Cerundolo, R., et al., Treatment of Canine Alopecia X with Trilostane. Vet Dermatol, 2004. 15(5): p. 285-293.

Ashley, P.F., et al., Effect of oral melatonin administration on sex hormone, prolactin, and thyroid hormone concentrations in adult dogs. J Am Vet Med Assoc, 1999. 215(8): p. 1111-5.

Frank, L., R. Donnell, and S. Kania. Estrogen receptor evaluation in Pomeranian dogs with hair cycle arrest on melatonin. in Nt Am Vet Derm Forum. 2006. Palm Springs.

Sieber-Ruckstuhl, N., et al., Cortisol, aldosterone, cortisol precursor, androgen and endogenous ACTH concentrations in dogs with pituitary-dependant hyperadrenocorticism treated with trilostane. Domest Anim Endocrinol, 2006. 31(1): p. 63-75.

Cerundolo, R., et al., Treatment of canine Alopecia X with trilostane. Vet Dermatol, 2004. 15(5): p. 285-93.