Introduction

Alopecia X is a disorder on which so much as been said and written but for which little is really known or understood. This name was coined a few years ago to refer to the following disease(s): pseudo-Cushing, adult onset growth hormone deficiency, hyposomatotropism of the adult dog, growth hormone responsive alopecia, castration responsive dermatosis, gonadal sex hormone alopecia, sex hormone/growth hormone dermatosis, hypogonadism in intact males, biopsy responsive alopecia, post-clipping alopecia (of plush-coated breeds), adrenal sex hormone imbalance, adrenal hyperplasia syndrome, Lysodren responsive dermatosis, follicular dysplasia of Nordic breeds, Siberian husky follicular dysplasia, follicular growth dysfunction of the plush-coated breeds and black skin disease of Pomeranians. The diversity in names are merely descriptive and based upon the differences in endocrine evaluation results and/or clinical responses to various therapeutic modalities.

Clinical Features

Initial clinical signs consist in loss of primary hairs (with retention of secondary hairs) in the frictional areas (around the neck, caudomedial thighs and tail). Gradually, all hair is lost in those regions and eventually the trunkal primary hairs are also lost, giving the remaining coat a puppy-like appearance (or very old sheep skin-rug appearance). With time (several months to years) the secondary hairs become sparse, and hyperpigmentation of the exposed skin and/or color change in the remaining hair coat may be seen.

The head and legs are usually spared.  A tendency to regrow hair at the biopsy site following skin biopsy or other external traumatic stimuli (skin scraping, sunburn, etc.) is a common finding in this syndrome.

The age of onset is from 9 months to 11 years (more often young adult). It is seen more frequently in neutered dogs. Breeds more at risk of developing this syndrome are the Nordic breeds with plush coat such as Pomeranians, Chow Chows, Keeshonds, Samoyeds, Malamutes and Huskies. Miniature Poodles seem also predisposed to this disorder.

	Figure 1a and b. (left and below) Chow Chow with alopecia X.
	Figure 2a and b. (left & right) Miniature poodle with alopecia X.

Etiopathogenesis

Etiopathogenesis of alopecia X remains obscure. A genetic predisposition to an unidentified hormonal imbalance and/or a change in receptor sensitivity at the hair follicle level is plausible. If the problem was a primary disorder of the hair growth cycle, various stimuli (including different hormones) could draw hair follicles into anagen phase.

Alopecia X, which occurs most commonly in breeds bred for hirsutism, may be caused by a primary follicular defect, similar to male pattern baldness, but with a sex-hormone related signal for expression. Indeed, men with pattern baldness do not always have elevated sex hormone concentrations; instead their hair follicles respond abnormally to a normal hormonal signal (e.g. receptor problems).

It also is possible that miniature Poodles (anagen based hair growth cycle) have a different clinicopathological entity than the plush-coated breeds (telogen based hair growth cycle). Ironically, however, it was found recently in a retrospective evaluation of adrenal hormone panels that adrenal sex hormone levels in miniature Poodles most resemble Pomeranians (Frank and others 2002).

It was recently suggested that the alopecia may be due to a mild but prolonged increase in basal cortisol concentration, instead of adrenal sex hormone imbalance (Cerundolo 2001a). This postulated pathogenesis is based on work done in miniature Poodles and Pomeranians with alopecia X which had increased urinary cortisol/creatinine ratios although normal post-ACTH stimulation cortisol levels.

Differential Diagnosis

This includes hypothyroidism; hyperadrenocorticism (natural or exogenous); sex hormone imbalance due to functional gonadal neoplasms; telogen defluxion, other follicular dysplasias and sebaceous adenitis.

Diagnosis

The diagnosis is based on history, physical examination findings, ruling out of other diseases (e.g. hypothyroidism and hyperadrenocorticism), skin biopsies and response to therapy. No specific hormonal diagnostic tests are currently available.

Histopathological examination of skin biopsies reveals changes consistent with endocrinopathies. Decreased amount and size of dermal elastin fibers were reported (chronic cases) in initial reports of growth hormone deficiencies. Later, the presence of "flame follicles" (excessive tricholemmal keratinisation) gained popularity over the elastin fibers. It is not known whether the flame follicle is simply a nonspecific expression of follicular growth arrest in these plush-coated breeds, or whether haircoat abnormalities featuring flame follicles are united by a common etiopathogenesis. However, even if flame follicles are neither pathognomonic nor observed in every cases of alopecia X, histopathologic evaluation should confirm atrophic/endocrine changes and rule out other disorders such as sebaceous adenitis or black hair follicular dysplasia.

An ACTH stimulation test measuring various reproductive hormones before and following ACTH administration have been proposed. However, the main limitation to the routine use of this testing is the cost and difficulty in details of shipping. In addition, the results are often inconsistent. Moreover, even when an abnormality is demonstrated (after hypercortisolemia is ruled out), it rarely changes the treatment approach or the outcome. Indeed, hypercortisolemia must first be ruled out because it was recently demonstrated that concentration of one or more adrenal sex hormones were substantially greater than reference range values before and after administration of ACTH in neutered dogs with hypercortisolemia (Frank and others 2001). Therefore, these hormonal assays may be more useful in trying to understand alopecia X than in guiding treatment for a specific patient.

Treatment

Once hypothyroidism and hyperadrenocorticism have been ruled out, the following approach is usually recommended. In an intact male, the first recommendation is castrate the dog. Most dogs will regrow a normal hair coat either permanently or for several months to several years. Although less frequently encountered in intact female dogs , this syndrome may also respond to ovariohysterectomy.

In neutered animals, various treatment modalities such as exogenous estrogen, testosterone or growth hormone can be administered. However, these therapies are no longer very popular due to either adverse effects, cost, availability and/or poor effectiveness.

O,p'-DDD (Lysodren®) is a relatively effective alternative when administered at 15-25 mg/kg, once daily for 5 days, then every 7-14 days as maintenance (lower dose than for Cushing's disease). Owners must be warned of the potential side effects (hypoadrenocorticism) before initiating this treatment.

Recently, new drugs have been used in an attempt to stimulate hair regrowth in dogs with alopecia X. Leuprolide acetate, an antigonadothropin, has been used with success in a dog with alopecia X. However, this drug is expensive and is only administered by intramuscular injection. L-deprenyl (Anypril®), a dopamine agonist has been use in 9 Pomeranians without success.

Trilostane, a competitive inhibitor of β-hydroxysteroid dehydrogenase, which interfere with adrenal steroidogenesis, has also produced encouraging results in Pomeranians and miniature Poodles (Cerundolo and others 2001b). The use of non specific dermatological therapy such as L-cysteine and D1-alfa-tocopheryl nicotinate was also proven to be effective in 50% of affected Pomeranians.

The efficacy of finasteride in alopecia X is being evaluated in a pilot study. Finasteride, is a synthetic specific inhibitor of type II 5 α-reductase, an intracellular enzyme that converts testosterone to dihydrotestosterone, resulting in a significant decreases in serum and tissue dihydrotestosterone concentrations in humans and in dogs (Kaufman and others 1998, Kamolpatana and others 1998). Finasteride has no affinity for the androgen receptor and has no androgenic, oestrogenic, antioestrogenic or progestational effects. In men with androgenic alopecia, the balding scalp with its miniaturized follicles contains increased amounts of dihydrotestosterone compared with the nonbalding scalp. Oral admninistration of 1 mg of finasteride daily decreases scalp and serum dihydrotestosterone concentrations, and promote hair growth although continued daily use of finasteride is needed in man for sustained benefit. Finasteride has been used in the treatment of prostatic hyperplasia in man and in dogs and appears to be safe. It has been taken (5 mg/day) for more than 7 years by millions of men to treat prostatic enlargement and no long term side effects are seen. Currently the drug is even being studied in healthy men as a possible treatment to prevent prostate cancer.

Melatonin, has been used by several veterinary dermatologists over the last few years in several dogs with alopecia X. It has apparently been successful in approximately 33% of the cases. Therefore, in spite of this modest success rate, melatonin is a valuable therapeutic alternative to try because of its safety and low cost. The hair growth observed in alopecic dogs treated with melatonin might be due to either modulation of sex hormone levels, interference with cortisol production, action at the hair follicle level by blocking estrogen receptors (estrogen can inhibit anagen initiation) or actual melatonin deficiency. However all of these proposed mechanisms are based on generalization of work done in other species.

Prognosis

Historically, due to cost, availability and/or side effects related to various treatments, owners often choose not to have their dogs treated, since alopecia X is only an esthetic problem. Moreover, it is important to state that benign neglect is considered a valid management alternative. Rather then promoting aggressive treatments (e.g. O,p'-DDD), one's efforts should be toward client education and promotion of acceptance of the alopecia (i.e. buy your dog a sweater).

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